- Disciples of the Ancient One (Only appearance)
- Ancient One (Yao) (Only appearance; dies)
- Frank (Sewer worker) (Only appearance)
- Demons of Dormammu (Only appearance)
- Cory (Dr. Strange's assistant) (Only appearance)
- Oliver (Hospital administrator) (Only appearance)
- Dr. Gina Atwater (Only appearance)
- Camille Carranza (Only appearance)
- Mrs. Carranza (Camille's mother) (Only appearance)
- April Strange (Only appearance; dies) (Only in flashback)
- Dr. Don Blake (Only appearance) (Cameo)
- Abraham Cornelius (Has a check made out to him) (Only appearance)
- Clea (Mentioned)
- Earth-2772 (Only appearance)
- Earth (Only appearance)
- United States of America (Only appearance)
- Germany (Only appearance)
- Australia (Only appearance)
- Hong Kong (Only appearance)
- Tibet (Only appearance)
- Nexus (Only appearance)
- Dark Dimension (Only appearance)
- Earth (Only appearance)
Dr. Stephen Strange is one of the most gifted surgeons in the world, however, he is also highly arrogant and dismissive of his colleagues. While driving home from the hospital one night, he notices Baron Mordo and his allies slaying a monster – notable because they are hidden from view by one of Wong's spells. An unbelieving Strange dismisses it as a stress-related hallucination. The next day, he is visited by the hospital's administrator Oliver who states that Dr. Gina Atwater has problems with him. He then speaks with Dr. Atwater and discusses her case of a child – one of many – who is suffering from dangerous nightmares. Seeing the children causes Stephen to flash back to when his sister April had a headache similar to the ones the children have experienced. The conversation also reveals that the two doctors have had a romantic relationship in the past. When touching one child, he sees an image of a laughing demonic skull engulfed in flames and promptly leaves, telling Atwater that there is nothing he can do for the children.
While driving home, Strange again sees the vision of the demonic skull and swerves his car to avoid ghostly children in the road, careening off the cliffside. As a result of the crash, his hands are permanently damaged, ending his surgical career. Strange spends his life savings in pursuit of a way to fix his fractured hands, but to little avail. The dejected doctor believes all is lost until his suicide attempt is thwarted by Wong, who suggests that the Ancient One is capable of offering him real hope, if he can make the journey to Tibet.
After begging Atwood to help him get to Tibet and then undertaking a grueling hike up into the Himalayas, Strange begins his training at a hidden monastery under the tutelage of the Ancient One — a diminutive old man. Soon after Strange arrives, the other students leave to combat a pack of wolf-like creatures in Central Park. Not long after, the Ancient One is told by Wong and Baron Mordo that some of the students died during the conflict. The conversation indicates that the number of assaults by mystical creatures has been growing recently. After spending several days scrubbing floors and performing manual labor, Strange becomes frustrated and determines to leave the monastery. As he walks through the snow, however, he has a flashback to a previous failure — when he performed surgery on his sister in an attempt to remove the brain tumor causing her headaches. During the procedure, April died and Strange has always blamed himself. The Ancient One appears in Stephen's mind and convinces him to let go of this past guilt and return to the monastery and further his training.
The next day the Ancient One detects two Chinous (reptilian monsters the size of a small house) approaching the sanctuary and orders Baron Mordo to kill them one at a time. However, the arrogant Mordo disobeys and leads two separate teams to take them on. As a result, several of the weaker students are killed before the beasts are defeated. Later as the Ancient One mourns the loss of his disciples, he scolds Mordo for his disobedience and tells him that he will never inherit the title of Sorcerer Supreme. The Ancient One then names Strange as his heir apparent. An angered Mordo later spars with Strange, escalating the mock-fight into a deadly contest of skills. During the fight, Strange instinctively absorbs Mordo's spell and deflects the energy back towards him. An enraged Mordo lunges to kill him, but Wong intervenes and tells Strange that he will be taking over the training. A dejected Mordo leaves, now with true hatred in his eyes for Strange.
Later Stephen follows the Ancient One, Wong, Baron Mordo, and the few other remaining students to the Sanctum Sanctorum - a nexus between realities that outwardly appears to be a New York City townhouse. The Ancient One then tells them about Dormammu, an ancient being that wishes to rule all worlds — especially Earth. Thousands of years ago, after Dormammu's previous bid at conquest, the Ancient One trapped him in a dimension of limbo. Upon seeing the visage of Dormammu, Strange recognizes it as the burning face and realizes that the demon is using children's dreams to enter Earth. Strange returns to the hospital and puts Atwood to sleep. He then searches her computer to find out how widespread the children's comas are. He awakens patient after patient to prevent Dormammu from entering Earth. Mordo also enters a child's dream and makes a deal with Dormammu, pledging to serve him in exchange for dominion as Earth's the Sorcerer Supreme. Dormammu takes over the minds of the remaining children as Mordo attacks Strange in the physical realm. Wong appears, however, and manages to save him.
As this is going on at the hospital, the Ancient One and his three remaining students attempt to ward off a swarm of Wing Marks — vicious flying mouths capable of stripping a person to the bone in seconds. All of the followers are killed and the Ancient One is left greatly weakened due to both exertion and old age. The traitorous Mordo then arrives to attack the Ancient One. When Strange and Wong late arrive at the Sanctum Sanctorum , they find the Ancient One dead. Wong gives Strange the Eye of Agamotto — a powerful symbol of the office of Sorcerer Supreme — and states that the position is Doctor Strange's destiny. Strange and Wong then confront Mordo. As Wong fights Mordo, he is wounded in battle, but Mordo is repelled by Strange. Strange then fights him as Dormammu begins his emergence into earth's physical dimension.
Dormammu immediately devours Mordo and steals the Eye of Agamotto as he makes his way to the Sanctum Sanctorum. Strange confronts Dormammu who begins to overwhelm the new sorcerer as he unleashes his monsters around the world. The wounded Wong, watching from nearby, reminds Strange of his experience sparring with Mordo and the Doctor then absorbs the pure magic the demon is blasting him with. Since the demon himself is made of pure magic, he soon vanishes into nothing after pouring his power into Strange. An astonished Wong states that he didn't expect Strange to actually absorb Dormammu but it will work.
Later, as they return to the Sanctum Sanctorum, Wong tells Strange that the primary purpose of the Sorcerer Supreme is to protect the Earth from mystical attacks such as the one they just experienced. Strange later appears in Atwood's dream, surprising her with his newfound humility and reassures her that all will be well with the children. Now dressed in the robes of his office, Strange visits his sister's grave to say goodbye and is told by Wong that they have new potential students to train. One of those who shows real potential is a girl named "Clea." Strange and Wong enter the Sanctum Sanctorum, closing the door behind them.
- Bryce Johnson as Doctor Strange
- Kevin Michael Richardson as Mordo
- Paul Nakauchi as Wong
- Fred Tatasciore as Oliver
- Susan Spano as Gina Atwater
- Jonathan Adams as Dormammu
- Tara Strong as April Strange
- Michael Yama as the Ancient One
- John Keaton as Corey
- Phil LaMarr as Miro
- Masasa Moyo as Adena