The story begins with a birth. Wanda Maximoff, also known as the Scarlet Witch, is surrounded by friends and family while giving birth. Her attending physician, Doctor Strange, hands Wanda her newborn twins and declares the birth a great success. At Wanda's side is her husband, The Vision, who is very proud of his wife and children. From across the room comes a cold and distant voice -- that of Professor Charles Xavier, who demands Wanda return the world to normal. She refuses, clinging to her babies, who shatter and disappear. There are no friends, no family and certainly no babies. Instead, Wanda is resting in a dark room in the devastated mutant paradise of Genosha. Using his fantastic mental powers, Professor X forces Wanda to sleep. Magneto appears, dressed humbly, and asks Professor X about his progress with his daughter. Professor X informs Magneto that his power will no longer be enough to hold back Wanda and that a solution must be found. Magneto, blaming himself for twisting his children through the strength of his own dreams and ambitions, walks on a magnetic field towards the center of the island to be alone.
Meanwhile, Xavier arranges a meeting of superheroes to decide the fate of Wanda Maximoff. Calling the Avengers, the X-Men and several lone heroes, a meeting ensues high atop Avengers Tower, presided over by Professor X himself. Emma Frost, reading the minds of all those in attendance, concludes that killing Wanda is the only way to end her destructive magic. Captain America, however, argues that the group should seek alternate methods of dealing with Wanda including suppression of her powers and her insanity. The X-Men argue that if word about Wanda and her destructive powers gets out, it will set back human-mutant relations by centuries. As the conversation progresses, it is revealed that Professor X asked Doctor Strange to help Wanda, but unfortunately neither was strong enough to combat her magic. Wolverine speaks up, saying that there is no other way -- Wanda must be killed. The rest of the group, however, decides that they must talk to Wanda in person before making their decision.
Back in Genosha, a distraught Quicksilver rushes to Magneto and reveals that he was just in New York where he heard that the X-Men and Avengers are planning on killing Wanda. Magneto angrily replies that he does not know what to do. Quicksilver falls to the floor sobbing and Magneto glances over at his sleeping daughter.
Xavier takes the two groups to Genosha, only to discover that Wanda is missing. Suddenly, the members of the group start to disappear one by one. Spider-Man is soon the only one left and becomes engulfed by a white light...
When the light departs, we see that the world has changed: Spider-Man is married to Gwen Stacy in New York; Cyclops and Emma Frost are married; Doctor Strange is a psychologist; Carol Danvers -- known usually as Ms. Marvel -- is now Captain Marvel, America's most beloved superhero; Gambit is a criminal; and Steve Rogers is an aged veteran. As we follow vignettes of their lives, it becomes readily apparent that none of them remember the change. Meanwhile, Wolverine, who is now in charge of the S.H.I.E.L.D. House of Magnus Red Guard, wakes up onboard a helicarrier sleeping next to Mystique. Unlike his comrades, Wolverine remembers.
Attempting to make sense of the strange world he finds himself in, Wolverine first seeks Professor X at the Xavier Institute for Higher Learning. He finds, however, a family who has lived in the mansion for fifteen years and who have no recollection of any Charles Xavier. Wolverine then sets out to find either Peter Parker or Tony Stark, the Iron Man. However, when he reaches the lobby of Stark Tower, he is stopped by his teammates in the elite Red Guards. He escapes, but is promptly contacted by his former New Avengers teammate, Luke Cage, when he is transported to the hideout of the "Human Resistance Movement" by Cloak. To make matters even stranger, he is then threatened by Hawkeye.
After enduring a less than pleasant security check from Hawkeye, Wolverine realizes that the Red Guard has followed the tracking chip that Hawkeye just removed from his neck. The room explodes and Wolverine's teammates storm the underground headquarters. In the middle of the battle, Cloak teleports everyone he can to the Kingpin's office, which he knew would be empty. There, Wolverine relates to the Sapien Underground Resistance the series of events that led to the establishment of this alternate world, including the Scarlet Witch's nervous breakdown and the subsequent murders of Hawkeye, Vision, Jack of Hearts, and Ant-Man, resulting in the destruction of the Avengers. Wolverine theorizes that his personal history under the Weapon X Program had so drastically wiped clean his memory that he alone could remember how things were. Furthermore, Wolverine asserts that as of yesterday he could remember every day of his life, and that he had what he most desired. Eventually Wolverine hypothesizes that Magneto used his daughter to give everyone what they wanted, so that the Master of Magnetism could have what he wanted -- global domination and a world where mutants dominate over the common man.
An incredulous Luke Cage asks how did Magnus know what they wanted; Wolverine simply states that Charles Xavier, whom Magneto had kidnapped prior to the final transition into the House of M, would have the power to ascertain these desires. When Wolverine questions if the group believes his story, they say that yes, they do. Questioning why they believe him so easily when his story is so fantastic, Wolverine is presented with young Layla Miller, a mutant girl in the alternate world who awoke that morning to realize she had the power to show people the real world. Wolverine decides that the best way to proceed is to get all his former teammates together to kill Magneto and the rest of the House of M. Wolverine and the resistance then arrive, via Cloak's transporting power, at Emma Frost's home; Wolverine asks the young girl known as Layla Miller to "enlighten" Ms. Frost, just as she had previously done with Luke Cage. It is still unknown why Layla remembers the world before the change, but it is believed she is a mutant with the ability to see alterations in reality.
Having illuminated Emma Frost, the resistance movement then contacts various heroes, including Cyclops, Shadowcat, Spider-Man, Rogue, Mystique, Nightcrawler, Toad, She-Hulk and Daredevil. As Layla awakened the heroes Rogue, being distraught and confused, touched Layla; the power appeared overwhelming for Rogue as it emanated from her and awakened others in the vicinity. Hawkeye, unable to handle reliving his own death, flees the group, and is seen again in The Pulse #10 acknowledging his own death. The group considers reawakening Captain America, but appears to decide against it, seeing that, in this reality, Steve Rogers was never frozen during World War II, is now roughly in his early eighties, and thus unable to aid them in the fight against Magneto. Meanwhile, in Genosha, Lord Magnus ignores his daughter, Lorna, in order to look at a memorial gravestone in the Genosha gardens that commemorates the death of Professor Charles Xavier.
Meanwhile, the 'awakened' heroes travel to the S.H.I.E.L.D. helicarrier where Emma Frost uses her mental powers to commandeer a vehicle to take them to Genosha. While travelling, the heroes sit down in the ship's cafeteria to enjoy a meal. While there, Cyclops informs the team that since the upcoming battle with Magneto may be the most important battle of their lifetimes, no one should restrict themselves or hold back in the least. This causes Jessica Drew to object -- if Magneto has given each of them everything they've ever wanted in this illusion, shouldn't they be content to just live in his world? Wolverine quickly dismisses the idea.
Back in Genosha, Magneto receives the incoming representative from Latveria, Victor Von Doom. There is to be a great event held that night to commemorate the mutant triumph over humanity, an event for which the House of M will act as host. Magneto and Doom smile and pose for the cameras, but it's clear that there is no love lost between the two. The party begins in the royal Magnus palace as the guests are introduced: King T'Challa (also known as the Black Panther) of the African Commonwealth of Wakanda, King of Latveria Victor Von Doom, Genis-Vell (a visiting delegate from the Kree Empire), Princess Ororo (also known as Storm) of Kenya and King Namor of the Kingdom of Atlantis. Finally, the hosts of the evening are introduced: the House of Magnus, comprised of King Erik Magnus, the Princess Wanda, Prince Pietro, Princess Lorna and Erik's two psychic grandchildren. Suddenly, from high above, a S.H.I.E.L.D. Sentinel plunges towards the castle. Magneto uses his magnetic powers to hold the Sentinel back from crashing into the castle when our awakened heroes attack. Leading the attack are Wolverine, Daredevil, Nightcrawler and Spider-Man. From the back, Cyclops calls out Magneto's name. When he turns, Cyclops unleashes a furious optic blast, apparently vaporizing Magneto on the spot. Rogue, finally able to unleash her powers to their full extent, tackles both Namor and Princess Ororo and absorbs their abilities, causing her to overflow with power.
Elsewhere, Cloak transports Emma Frost and Layla Miller to Magneto's Genosha garden. Searching for Xavier, they instead find the memorial commemorating his death. Emma Frost collapses to the ground weeping, crying out that "It's all over!" Suddenly, Cloak fades into the ground and reemerges, revealing that Xavier's remains aren't in his grave.
The battle between the House of M and the heroes continues with great ferocity. While the chaos ensues, the Scarlet Witch disappears from the battlefield only to be discovered by Dr. Strange in a tower with her children. The two begin to talk as Dr. Strange attempts to discover the origin of the madness that is happening. Wanda reveals the answer to him in a flashback to the beginning when Quicksilver is confronting Magneto about the fate of Wanda. It turns out that Quicksilver himself was the one responsible for the creation of the alternate world, conspiring with Wanda to make everyone happy in an almost perfect world. After this revelation, Emma Frost tells Strange to ask about the fate of Charles Xavier, but before he can Wanda is struck in the back by an arrow.
The attacker is Hawkeye, who begins to break down emotionally to Wanda about his death in the real timeline. After a heated exchange, Hawkeye is killed for the second time as one of the Scarlet Witch's antagonized sons - who, as in Avengers Disassembled, are both conduits for Wanda's own troubled mind - uses his mutant powers to make the poor avenger non-existent again. Meanwhile in the memorial garden, Magneto confronts Emma Frost and Layla Miller, who reveals the truth to Magneto about all that has happened. He then unleashes his wrath on everyone, especially his son Quicksilver. He nearly kills Quicksilver by pummeling him to a bloody pulp with large pieces of steel. Suddenly the Scarlet Witch appears, stopping Magneto and returning her brother to healthy form. She begins to lash out saying, "We're freaks, Mutants... you chose this over us and you ruined us..." Then, with four words, "Daddy... No More Mutants", things begin to break down and everything burns out to white once again.
With a blinding flash, the world seemingly came back to the way it was. New York was back to normal when Layla Miller woke up from what she thinks must have been a lucid dream where she played an important part.
Peter Parker woke up confused with Mary Jane Watson at his side. Together with the Avengers, they tried making sense of what happened that night -- some of them remember, some don't -- only to be confronted by a distraught Doctor Strange bringing in the fact that the House of M really took place and its effects are slowly being felt on a wider scale.
Outside of the X-Mansion, Emma Frost woke up with her nose bleeding. Screams came pelting from the mansion as the students of the Xavier's School for Higher Learning one by one faint and lose their powers. Two confirmed students to lose their powers are Wind Dancer and Tag from New X-Men: Academy X. Helplessly, the X-Men watched most of their students lose their gifts, hoping in vain that Emma would soon give them an answer to all their questions. As Nightcrawler raced to find Wolverine, Emma Cerebra-scanned the whole world for Mutant activity only to find out the great decimation the mutant population has endured and among them depowered is a sweating Iceman, Bobby Drake. Meanwhile, Wolverine awoke remembering everything about his past.
Back at the Stark Tower, the Avengers sought possible explanations from whatever useful sort of media report they could get when they are interrupted by an abrupt appearance of someone in the Mansion's ruins. What they saw when they came there was Hawkeye's uniform and an article written by Kat Farell publicizing his death, leaving tears and a great sense of pride among his former teammates.
- Note: One of the news channels seen on the TVs shows an outdated photo of Marrow for unknown reasons.
Still in desperate pursuit of answers, the X-Men fly to Genosha to confront Magneto who also lost all his powers. He was not able to satisfy them with the answers they've been seeking, and for all his past evil deeds, Wolverine decides to keep him alive to live the life of a powerless, and aging normal human: the kind of person Magneto never wished to be.
Whatever caused the majority of the mutant population to lose their powers, the heroes can only guess. With Xavier still missing, and with the Scarlet Witch probably depowered (as she could not be detected by the Cerebra scanner or by Doctor Strange and she later appears to be living a normal life), the mutant population can only hold on to Hank Pym's word that all these powers could not simply vanish... they are contained somewhere; and that for every action, there's an equal and opposite reaction. The question remains, as Hank Pym said, "What will be the reaction?"
As if to punctuate this statement, a colossal red ribbon of energy begins to orbit Earth...
Characters who have gone through changes include:
- Captain America: Steve Rogers is now an aged veteran who obviously did not live through a suspended animation period like the mainstream Captain. He lives in an apartment building in a Bronx neighborhood where it seems he's the only human, probably a privilege won from his service in WWII as Captain America. His long-dead sidekick Bucky, survived the fatal accident at the end of World War II, only to die later under mysterious circumstances in the 1970s as a part of a covert S.H.I.E.L.D. strike upon Genosha. Steve Rogers publicly quit being Captain America in 1950 when being grilled by Joseph McCarthy on his public association with known mutants and fellow Invaders, Namor and Toro, but still had enough influence to be the first man to walk on the moon 2 years later. Rogers' outspoken campaigning first against anti-mutant prejudice and then the rising fascism of Magneto has marginalized him into near obscurity nowadays.
- Iron Man: Tony Stark is the owner of Stark Enterprises, a company given to him by his father. He is a winning contestant on 'Sapien Death Match', a reality TV/wrestling show which involves humans in power-armor battling each other. He lives in the shadow of his father, and has been developing a superior armor to protect himself. Iron Man earned the admiration of human and mutant alike, including Magneto himself, when he and a team of Sapien Death Match fighters stopped a terrorist plot to kill hundreds of mutants with 'gene bombs.'
- Spider-Man: Peter Parker is having the time of his life as a famous pro wrestler. He lives in a big condo with his wife Gwen Stacy and son and having Rhino as a bodyguard. He also owns a corporate empire that recently acquired Oscorp. Albeit this luxurious life, Peter is living with the burden of a lie because the public doesn't know that his powers were not a mutation. He's using his wealth to protect his family, who also includes Uncle Ben, from the racist world. Flash Thompson is a commentator on Sapien Death Match. Mary Jane Watson has become a famous actress.
- X-Men: The X-Men, as an organisation, does not exist. Scott Summers and Emma Frost are married and living in Connecticut. Emma is a social worker who is seeing the now orphaned Franklin Richards. Hank McCoy is a scientist working with Hank Pym for Stark Industries. McCoy tends to mollify the increasingly isolated Pym, who suffers from anti-human racism, in order to protect him from harm. Remy LeBeau is a petty thief (who is quickly apprehended by Carol Danvers), while Storm is a Kenyan princess, and Shadowcat (Kitty Pryde) is a junior high history teacher. Dazzler (Alison Blaire) has a popular daytime talk show, although she is possibly suffering from a disease which is causing her light-show powers to fade. Colossus lives happily on a Russian farm. Professor Xavier "died so Genosha could live" and never founded the X-Men - although the exact circumstances of his death and its plausibly implied he never actually existed in this world due to his grave being empty. Time-displaced characters are also accounted for in the House of M world. Bishop is a police detective in New York City, Cable is an infant raised by Mr. Sinister, and Marvel Girl is a close friend of Psylocke, who is a member of the British royal family. Both Psylocke and Marvel Girl discover a quantum tear in a lighthouse shaped like an "X". Along with Captain Britain and Nocturne, they must seal this breach to save their universe. So far, Wolverine, who is part of S.H.I.E.L.D.'s elite Red Guard, and having an affair with Mystique, seems to be the only one who knows something is wrong in this world. He was actually affected to gain his "one true desire" and now remembers his entire life. Mystique's two children, Rogue and Nightcrawler are also members of the elite squad.
- Avengers: With Captain America a retired old man, the Avengers might as well never came to be or had a short life without his presence. Henry Pym is a disenfranchised worker in Stark Industries, Tony Stark is an industrialist, and Janet Van Dyne is a fashion designer: none of them know each other. Wonder Man is a famous actor who is rumored to have an affair with Ms. Marvel, aka Carol Danvers, America's favorite superheroine. The Sentry is a disturbed father seeing Dr. Strange helping him with a nightmare he's been having. Luke Cage is an underworld boss who is questioned about Wilson Fisk's beating the night before by unpopular detective Sam Wilson. Hawkeye is alive in this reality, and working with Luke Cage. The Vision is an experiment by Stark Enterprises. Spider-Woman (Jessica Drew) is a member of the Red Guard. Natasha Romanov is also an agent of S.H.I.E.L.D. Black Panther controls a number of African nations apparently in a union with Storm. Other Avengers are unaccounted for at present.
- Fantastic Four: Reed Richards and Sue Storm mutated and died in a rocket explosion along with John Jameson, the son of J. Jonah Jameson. The only survivor was Ben Grimm, leaving Franklin an orphan. Johnny Storm is a contestant on 'Sapien Death Match', where his power-armor has a 'Flame On' ability. Doctor Doom has a liquid-metal body and leads a group called the Fearsome Four (other members include Valeria (not Marvel Girl, but Doom's wife) as The Invincible Woman, Kristoff Vernard (Doom's adopted son and possibly the half-brother of Reed Richards) as the Inhuman Torch, and Ben Grimm as the It). Other than Grimm, all members of the group received their powers from Doom's experiments on the corpses of Reed and Susan Richards.
- Cable & Deadpool Vol 1: During the "Enema of the State" story arc, Cable fought an evil entity and ended up missing. Although everyone presumed Cable to be dead, Deadpool ironically believes him still alive and asks Forge to create a device in order to track Cable down. With Siryn and Cannonball, Deadpool begins jumping from alternate earth to alternate earth finding many versions of Cable (in which he jokes, "what if Cable choose door number 2?"), from a Horseman of Apocalypse to an Utopian ruler. He finally reaches the real Cable, except that he is a baby and under the care of Mr. Sinister. When Deadpool finally grabs Cable, he unsuccessfully attempts to teleport out of the dimension, only to be impaled by Sinister. Deadpool, Cannonball, and Siryn are unaware that they are back in the regular Marvel universe, but that the world around them has been transformed thanks to the interference of the Scarlet Witch.
- Thunderbolts: Genis-Vell (Photon) is a private in the Kree Army, son of the celebrated Kree Hero Mar-Vell, living in his father's shadow. Abner Jenkins (MACH IV) is a scientist secretly working for the Human Resistance, along with Erik Josten (Atlas), who is part of an elite sapien military unit, the Howling Commandos, and Jim Sanders (Speed Demon). The three, along with General "Dum Dum" Dugan, are attempting to create a chemical weapon to wipe out all the Kree on Earth, so the humans can strike an alliance with the Shi'ar to overthrow the House of M. Dr. Chen Lu (Radioactive Man) fights alongside Baron Von Strucker against both mutants and Kree. Photon's Cosmic Awareness allows him to partially see through Scarlet Witch's alterations and use his powers to show other characters possibilities (particularly Josten). Without the ability to fully control his power, he presents a threat to existence itself. Jenkins and Josten unearth an old Atlas Class Sentinel, and use it against Genis, who is only defeated and put into a coma by the chemical weapon Sanders was developing, thus alerting the Kree to the human resistance's plot to destroy them.
- X-Men Villains: Apocalypse still exists in this reality and rules Egypt with his Horsemen after siding with Magnus. Mastermind has been mentioned as a business rival of Tony Stark. Exodus, Pyro, Unus the Untouchable and a mutant teleporter who may be Vanisher govern for the House of M in Australia, although they have recently fallen at the hands of an enraged Hulk. Sabretooth is an assassin apparently working for Magnus. Sebastian Shaw is director of S.H.I.E.L.D. and Magnus' "Red Guard". Captain John Greycrow (Scalphunter) and Commander Garrison Kane are also agents of S.H.I.E.L.D. Even the Weapon Plus Program serves the House of M and has created operatives up to Weapon XXXC. Blob and Phantazia are among the HOM servants in Genosha. The Marauders are a Black Ops Team lead by Callisto and composed of Sunder, T-Rex, Banshee, Mammomax, Black Tom, Caliban and the Blob. The Sentinels are controlled by the House of M and even Omega Sentinels serve the government.
- Other: Matt Murdock does exist as Daredevil and was caught kissing fellow lawyer Jennifer Walters (aka She-Hulk). Cloak (of Cloak and Dagger) is working for Luke Cage, with Danny Rand, Moon Knight, and White Tiger. Toad and Mystique are members of the Red Guard with Wolverine. Otto Octavius (Doctor Octopus) is working on stem-cell research for the government. Betty Brant and Kat Farell are working for the Pulse. Moira MacTaggert is the most wanted sapien on the planet for trying to undo her son's mutation and is framed for the deaths caused by her son. Kevin MacTaggert (Proteus in normal continuity) is also the most wanted mutant, known as 'Mutant X'. He has taken the body of Angel Salvadore, who is a rich model known widely. Kevin Plunder (Ka-Zar) has been granted political asylum in the United States for his human rights activism in 'Pangea', possibly the Savage Land. Bruce Banner is living with a tribe of Aborigines in Australia, where he is gaining mastery of his dual nature, and has been roped into AIM's resistance movement. Jessica Jones is living in Queens and is apparently dating a man named Scott. The Silver Surfer's whereabouts are unknown. Zebediah Killgrave has no powers, and is a lobbyist for the government, with secret affiliations with the Human Resistance.
- Unaffected Characters: Only Layla Miller appears to be aware of the changes wrought by Wanda. Layla restored the memories of several members of the Avengers and the most of the X-Men (notable exceptions include Captain America).
- House of M #1
- House of M #2
- House of M #3
- House of M #4
- House of M #5
- House of M #6
- House of M #7
- House of M #8
- Spider-Man: House of M #1
- Spider-Man: House of M #2
- Spider-Man: House of M #3
- Spider-Man: House of M #4
- Spider-Man: House of M #5
- Fantastic Four: House of M #1
- Fantastic Four: House of M #2
- Fantastic Four: House of M #3
- House of M: Avengers #1
- House of M: Avengers #2
- House of M: Avengers #3
- House of M: Avengers #4
- House of M: Avengers #5
- Incredible Hulk (Vol. 2) #83
- Incredible Hulk (Vol. 2) #84
- Incredible Hulk (Vol. 2) #85
- Incredible Hulk (Vol. 2) #86
- Iron Man: House of M #1
- Iron Man: House of M #2
- Iron Man: House of M #3
- Mutopia X #1
- Mutopia X #2
- Mutopia X #3
- Mutopia X #4
- Uncanny X-Men #462
- Uncanny X-Men #463
- Uncanny X-Men #464
- Uncanny X-Men #465
- Wolverine (Vol. 3) #33
- Wolverine (Vol. 3) #34
- Wolverine (Vol. 3) #35
- New X-Men (Vol. 2) #16
- New X-Men (Vol. 2) #17
- New X-Men (Vol. 2) #18
- New X-Men (Vol. 2) #19
- Exiles #69
- Exiles #70
- Exiles #71
- Excalibur (Vol. 3) #13
- Excalibur (Vol. 3) #14
- Secrets of the House of M #1
- The Pulse House of M Special #1
- Black Panther (Vol. 4) #7
- Captain America (Vol. 5) #10
- New Thunderbolts #11
- The Pulse #10
- Cable & Deadpool #17
- The event begins six months after Wanda's nervous breakdown and the apparent deaths of Hawkeye, the Vision, and Ant-Man in the Avengers Disassembled event. 
- House of M originated as an idea to fill-in a break in the release schedule of Astonishing X-Men, which had been requested by the title's penciler John Cassaday in order to be able to continue working on the title uninterruptedly.
- 2 minor appearance(s) of House of M (Event)
- 9 mentions of House of M (Event)
- 2 image(s) of House of M (Event)
- 61 article(s) related to House of M (Event)