America Chavez and a version of Stephen Strange are chased by a demon in the space between universes while searching for the Book of Vishanti. Strange is killed and Chavez accidentally creates a portal that transports herself and Strange's corpse to Earth-616, where that universe's version of Strange rescues Chavez from another demon with help from the Sorcerer Supreme, Wong. Chavez explains that the beings are hunting her because she has the power to travel through the multiverse.

Recognizing witchcraft runes, Strange consults Wanda Maximoff for help but realizes that she is responsible for the attacks. After acquiring the Darkhold and becoming the Scarlet Witch, Maximoff believes that controlling Chavez's powers will allow her to reunite with Billy and Tommy, the children she created during her time in Westview. When Strange refuses to surrender Chavez, Maximoff attacks Kamar-Taj, killing many sorcerers. Chavez accidentally transports herself and Strange to Earth-838, while Maximoff uses the Darkhold to "dreamwalk", taking control of her Earth-838 counterpart, who lives a suburban life with her own Billy and Tommy. A surviving sorceress sacrifices herself to destroy the Darkhold and break the dreamwalk. Enraged, Maximoff forces Wong to lead her to Mount Wundagore, the source of the Darkhold's power, to reestablish the dreamwalk.

While searching for help, Strange and Chavez are apprehended by Earth-838's Sorcerer Supreme, Karl Mordo, and brought before the Illuminati, a group consisting of Mordo, Peggy Carter, Blackagar Boltagon, Maria Rambeau, Reed Richards, and Charles Xavier. They explain that through reckless use of their universe's Darkhold in an attempt to defeat Thanos, Earth-838's Strange triggered a universe-destroying "incursion". After defeating Thanos, the Illuminati executed their Strange to prevent him from causing more harm. Mordo believes that Earth-616's Strange is similarly dangerous, but Maximoff reestablishes her dreamwalk at Mount Wundagore and arrives in her Earth-838 counterpart's body before they can pass judgment. She brutally kills all the Illuminati except Mordo, whom Strange subdues before fleeing with Chavez. The two escape with help from the Earth-838 version of Strange's ex-fiancé, Christine Palmer, a scientist working with the Illuminati.

Strange, Chavez, and Palmer enter the space between universes to find the Book of Vishanti, which is the antithesis of the Darkhold, but Maximoff appears and destroys it. She then takes over Chavez's mind, using her powers to send the others to an incursion-destroyed universe. Strange defeats the destroyed universe's Strange, who has been corrupted by his universe's Darkhold, and uses it to dreamwalk into the body of his deceased counterpart on Earth-616. With Wong's help, Strange saves Chavez from Maximoff as she tries to take Chavez's powers and encourages Chavez to use her abilities. She transports Maximoff to Earth-838, where she sees Billy and Tommy recoil from her in fear while crying for their real mother. Realizing the error of her ways, Maximoff relents and uses her powers to bring down Mount Wundagore, simultaneously destroying all copies of the Darkhold throughout the multiverse and apparently sacrificing herself in the process. Chavez returns Strange and Palmer to their respective universes.

Sometime later, Kamar-Taj is repaired and the surviving sorcerers, joined by Chavez, continue training.