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Nightcrawler, a teleporting mutant, attempts to assassinate the President of the United States in the White House, but he fails and escapes. Wolverine reappears after discovering nothing at Alkali Lake, while Storm and Jean find Nightcrawler with the help of Professor Xavier and Cerebro. Cyclops and the Professor visit Magneto in his plastic prison to see if he had any part in the attack on the president. Reading Magneto's mind, the Professor discovers that a covert government operative, William Stryker, has been extracting information from Magneto. A trap is sprung and Cyclops and the Professor are captured by Stryker and his assistant Yuriko Oyama. A military raid of the X-Mansion begins, with the soldiers sedating every student they find. Wolverine confronts Stryker, who fails to shed any light on his past.
Impersonating Senator Robert Kelly and Yuriko, Mystique gains information about Magneto's prison and provides a means for him to escape. Wolverine, along with Rogue, Iceman and Pyro, head to Iceman's (Bobby Drake's) parents' home in Boston. After a 9-1-1 call the police arrive just as the group is about to leave. The X-Jet arrives to pick them up and the X-Men team up with Magneto and Mystique. Magneto has learned Stryker orchestrated the attack on the president and has been experimenting on mutants, using a drug injected directly into the back of the neck to control them. Jean reads Nightcrawler's mind and determines that Stryker's base is located at Alkali Lake, inside the dam where he plans to kill the world's mutants by building a second Cerebro.
Through his son, Jason, Stryker gains control over the Professor. His son is able to project powerful visions in the mind, blinding a person to reality and through this the Professor is brainwashed to use Cerebro to find and kill all mutants. Mystique is able to infiltrate Stryker's base by impersonating Wolverine; the X-Men enter and Storm and Nightcrawler search for the kidnapped students. Jean, Magneto and Mystique are attacked by a brainwashed Cyclops while trying to rescue the Professor and in the process cause damage to the generators that keep the dam from collapsing. The force of Jean's telekinetic blast awakens Cyclops from his brainwashing and at the same time Wolverine finds Stryker in an adamantium smelting room along with Deathstrike. Wolverine manages to defeat Deathstrike and then finds Stryker on a landing pad, where Stryker attempts to bargain Wolverine for his life with stories of his past. However, Wolverine refuses, and returns to save his friends from the collapsing dam, leaving Stryker chained to the helicopter.
While disguised as Stryker, Mystique uses Jason to convince the Professor to kill all humans and Magneto and Mystique use Stryker's helicopter to escape Alkali Lake, chaining Stryker to concrete rubble. Meanwhile, Nightcrawler teleports Storm inside of Cerebro where she creates a snowstorm to free the Professor from his telepathic illusion. The dam bursts but a malfunction aboard the X-Jet prevents it from taking off. As the flood gets stronger, and Jean leaves the jet and creates a telekinetic wall in order to stop the wave and raises the jet above the flood waters. Jean activates the X-Jet's primary engines, before releasing the torrent of water down on herself.
The X-Men are able to supply the president with files from Stryker's private offices, and the Professor warns him that humans and mutants must work together to build peace or they will destroy each other through war. The film ends with a voiceover by Jean Grey on the process of evolution (a speech originally made by the Professor in the introduction of the first film). The camera floats over Alkali Lake, showing a vague shape of a Phoenix in the lake.
