A pharmaceutical company called Worthington Labs announces that it has developed an inoculation to permanently suppress the X-gene that gives mutants their powers, offering the "cure" to any mutant who wants it. While some mutants are interested in the "cure", including the X-Men's Rogue, many others are horrified by the announcement. In response to the news, the X-Men's adversary Magneto raises an army, warning his followers that the "cure" will be forcefully used to exterminate the mutant race.
Cyclops, still heartbroken about the loss of Jean Grey, returns to Alkali Lake, where Jean sacrificed herself to save the X-Men. Jean appears to Cyclops, and as the two kiss, Jean changes and appears to kill Cyclops. Sensing trouble, Professor Charles Xavier sends Wolverine and Storm to investigate. When they arrive, the two X-Men encounter telekinetically floating rocks, Cyclops' glasses, and an unconscious Jean.
Xavier explains that the majority of Jean's power is seated in her unconscious mind (Sigmund Freud's "Id") and that, as a result, her powers are largely fueled by instinct, and not under her complete control. In fact, when Jean was a little girl she was so powerful that he had to put telepathic blocks on her mind to help keep her powers under control. Her bottled up powers manifested themselves as an id-like alternate personality called the "Phoenix"--a purely instinctual creature, ruled not by logic, but by its own violent desires. Wolverine is disgusted to learn that Xavier has kept Jean in check telepathically, but when Jean awakens, he realizes she is not the Jean Grey he knew. Wolverine asks about Cyclops, but she cannot remember and fears she killed him. Jean pleads with Wolverine to kill her before she harms anybody else, but when he refuses, the Phoenix surfaces and telekinetically slams Wolverine into a wall. She then flees to her childhood home. Magneto, also aware that Jean's powers are loose, meets Xavier at Jean's house. The two men vie for Jean's loyalty until the Phoenix resurfaces, unleashing her devastating power. Furious at being caged within Jean's subconscious for twenty years, she destroys her family's house, disintegrates Xavier, and leaves with Magneto.
Following the losses of Xavier, Cyclops, and Rogue (who decides to take the mutant "cure"), the X-Men regroup and confront Magneto's army, which is attacking the pharmaceutical company's laboratory on Alcatraz Island. During the battle, Beast injects Magneto with the "cure", nullifying his mutant powers. After the battle, Wolverine nearly coaxes Jean back to sanity. However, soldiers arrive and fire upon Jean. The Phoenix quickly emerges and begins to destroy everything and everyone around her. While the other X-Men flee to safety, Wolverine fights his way to Jean, relying upon his healing abilities to save him from her destructive power. Momentarily gaining control, Jean begs Wolverine to save her. Telling Jean he loves her, Wolverine reluctantly kills her with his claws.
Despite the X-Men's losses, life goes on. The school will continue, even without Xavier. Rogue returns and tells Iceman she had to take the "cure." The two reconcile and continue their relationship now able to touch each other. Magneto, now an ordinary man, sits at a chessboard and reaches out toward a metal chess piece that trembles slightly — indicating that the cure might not be as permanent as thought. Following the closing credits, Dr. Moira MacTaggert checks on a comatose patient who greets her with Xavier's voice, implying that he has transferred his mind into this new body.
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