Doctor Octopus, Electro, Rhino, Kraven the Hunter, and Beetle have come together in Doctor Octopus' underwater lab in the Hudson River where they had captured Dr. Curt Connors.
When Spider-Man arrives to rescue Dr. Curt Connors, he is ambushed by Doctor Octopus and his villain allies as Doctor Octopus mutates Dr. Curt Connors into Lizard with the help of a control collar on his neck to be the sixth member of Doctor Octopus' Sinister Six. The Sinister Six then attack Spider-Man where Doctor Octopus mentions that he has jammed all the signals.
Unable to get through to his team, Spider-Man had to use some tactics in an echo tunnel to fool the Sinister Six and send them down different tunnels. When Spider-Man corners Lizard who temporarily changes back, Doctor Octopus reactivates the control collar on Lizard who knocks out Spider-Man as the rest of the Sinister Six arrives. When Doctor Octopus states that they should have Spider-Man unmasked to complete his revenge, Kraven the Hunter suggests that Lizard should do the honors of unmasking Spider-Man. As Lizard prepares to unmask Spider-Man, Doctor Octopus controls Lizard to remove Spider-Man's mask as Kraven the Hunter plans to do the job himself.
Lizard attacks Kraven the Hunter as Spider-Man tricks Rhino into flooding Doctor Octopus' lab. Spider-Man swims to the docks as the Sinister Six follows him. Spider-Man rides the helicopter to the Statue of Liberty as the Sinister Six catches up to Spider-Man. Things weren't looking good for Spider-Man when the Sinister Six make a comeback in their fight against Spider-Man. In the nick of time, Spider-Man's team arrives to help him fight the Sinister Six.
When Spider-Man has his team switch opponents, Spider-Man fights Doctor Octopus as Lizard breaks free from the control collar. Spider-Man then removes the control collar from Lizard. While Spider-Man's team watches over the other Sinister Six members until S.H.I.E.L.D., Lizard escapes into the sewers. The rest of the Sinister Six are arrested by S.H.I.E.L.D.
Return of the Sinister Six
An armored Doctor Octopus and Lizard invaded Ryker's Island and reassembles the Sinister Six by armoring up Electro, Kraven the Hunter, Rhino, and the new recruit Scorpion of K'un-Lun. The Sinister Six give Spider-Man a hard time until Norman Osborn in the Iron Patriot armor and the rest of Spider-Man's team arrives. While Spider-Man fights Lizard, Iron Patriot fights Doctor Octopus while Spider-Man's team fight the other members of the Sinister Six. When the Sinister Six end up combining their attacks to take down Iron Patriot, Doctor Octopus plans to inject Spider-Man with the Goblin Serum. Doctor Octopus then injects Norman Osborn with the Goblin serum while Spider-Man restored Lizard to Dr. Curt Connors. Norman Osborn becomes Green Goblin where he defeats most of the Sinister Six. Though Spider-Man has won against the Sinister Six, Green Goblin gets away with the captive members of Spider-Man's team. After the Sinister Six were defeated, Dr. Curt Connors thanks Spider-Man for saving him.
Hydra Alliance and the Sinister Seven
After Doc Ock joined Hydra to destroy Spider-Man and S.H.I.E.L.D., he started to look for potential recruits to finally have his win. He tried to recruit Boomerang, Vulture, Batroc, Shriek, Grizzly, Shocker and Beetle that betrayed Octopus or where defeated by Spider-Man and his team. Octavius also tried to recruit Norman Osborn to be the Goblin but he was immune to the serum, Dr. Connors into the Lizard but he was saved by Spider-Man, Sandman but he resisted to Doc Ock's mind control and finally I tried to recruit a new ally Harry Osborn transformed with a new symbiote into Anti-Venom but he went out of control and escaped Otto. Finally, Doctor Octopus found the perfect line-up for his Sinister Six consisting of Kraven, The Goblin from Miles's dimension, Electro, Hydro-Man, Rhino and himself. The attack was located on the roof of the Triskelion. At first, Spider-Man retreated but he was convinced by Ben to fight back. While S.H.I.E.L.D. Academy was winning the fight, Doc Ock went to the lab to find the Anti-Hydra weapon. After the defeat of the Sinister Six, Parker and Reily were trying to find Doc Ock but they were surprised by an attack of The Ultimate Goblin. After this Spider-Man, it was betrayed by Scarlet that was revealed to be the spy in S.H.I.E.L.D. and told Octavius that the key of the Anti-Hydra weapon was in Peter's Aunt May house.
On the day of graduation at S.H.I.E.L.D. academy, Doc Ock recruited Kraven and Scorpion back into his group, while brainwashing Vulture and Rhino into his service. He also turned Crossbones into a new Lizard. Spider-Man cured the three mutants, while Kraven and Scorpion were knocked out. Doc Ock turned himself into a monstrous octopus, but found his mind fading; he begged for help and was restored to normal.
- 11 members of Sinister Six (Earth-12041)
- 10 appearance(s) of Sinister Six (Earth-12041)
- 8 image(s) of Sinister Six (Earth-12041)