A blue-skinned, teleporting mutant attacks the White House and nearly kills the President before hes shot and retreats. Xavier collects the X-Men from a field trip, also interrupting new student John Pyro Allerdice from using his pyrokinetic power in front of humans, and as they try to track the new mutant down, Wolverine returns from the trip Xavier sent him on, having gotten no new information from the abandoned Alkali Lake base. For now, his search needs to be put on hold due to the current crisis.
Colonel William Stryker meets with the President and reveals hes learned from drug-aided interrogations of Magneto the truth about the School for the Gifted, and gets permission to launch an attack. Mystique, still posing as Kelly, meets with him and then sneaks into his office in the form of his assistant Yuriko, where she discovers the location of Magnetos cell, and also that Stryker has built his own Cerebro.
The new mutant finally stops his teleporting at a church in Boston, and Jean and Storm go to meet him. He introduces himself as Kurt Nightcrawler Wagner, a German circus performer who has only a vague recollection of making the attack. They notice a round scar on the back of his neck just like the one Magneto has.
Xavier and Cyclops go to see Magneto, who tells them about Stryker and how he had to tell everything. Just then, gas floods into the cell and knocks out Xavier and Magneto, while Cyclops is taken down by Yuriko, revealing shes also a mutant.
Strykers men next attack the school, with Wolverine as the only adult left to defend it. He and the students with useful fighting powers help many of the others to escape before Stryker arrives and reveals hes part of Wolverines unknown past. Before he can say any more, Iceman puts up an ice wall between the two of them, and Wolverine escapes with him, Rogue, and Pyro to meet up with Jean and Storm in Boston, Iceman noting thats also where his family lives.
Xavier is woken up by Stryker, who reminds him of his failed attempt to help Strykers self-loathing mutant son Jason. Upon returning home, Jason used his illusion power to drive his mother to suicide, causing Stryker to declare his son dead and lobotomize him. Now hes out to kill all mutants, and brainwashed Nightcrawler to attack the President as a pretext to get his hands on Xavier, so he can direct Jason to get Xavier to activate Cerebro.
Mystique seduces one of Magnetos guards, then drugs him and injects an extra dose of iron into his blood. When he arrives for his next shift, Magneto immediately detects it and pulls the metal right out of him, then turns it into projectiles to escape the prison.
Iceman takes the group to his familys house, and reveals to them that hes a mutant. His brother Ronnie calls the police, and Pyro escalates the ensuing standoff by throwing fireballs at them until Rogue takes his power and puts all the fires out. Just then Jean and Storm arrive in the teams jet and the others flee, but the Air Force is soon after them. Storm takes care of most of the pursuers with tornadoes, but one pilot manages to launch two missiles. Jean taps into a whole new power level that causes her eyes to glow orange, but can only destroy one and the jet is badly damaged by the other. Luckily, Magneto arrives and takes control of the jet, setting them down safely.
Magneto tells the group about Strykers plan, which theyll have to work together to stop, also revealing Stryker was behind the project that gave Wolverine his adamantium bones. Jean searches Nightcrawlers mind and discovers Stryker has gone back to his old base at Alkali Lake, and Mystique is sent in disguised as Wolverine so she wont be killed on the way in and can then take over the control room, letting the others in. Jean is attacked by a brainwashed Cyclops and again uses her new powers, which frees him but also damages the lakes dam.
Wolverine finds the room where he was experimented on, and is confronted by Yuriko, who reveals she also has adamantium claws and takes on her true identity of Lady Deathstryke. After a seemingly impossible fight between the two healers, Wolverine pumps her full of more adamantium, which kills her. He then confronts Stryker again, who reveals Wolverine actually volunteered for the procedure and did some very bad things for the project. The dam starts falling and Stryker offers the whole story if Wolverine will abandon the X-Men and save him, but Wolverine chooses his new friends and leaves him chained up to die.
Jason has put Xavier in an illusion to use Strykers Cerebro to kill all mutants, but Magneto breaks in and changes the order to kill all humans. He and Mystique take their leave, also bringing along Pyro whos decided to join him. To stop Jason, Nightcrawler is forced to make a risky no-sight teleport to bring Storm into the room, where she freezes everything and puts a stop to the illusion.
The X-Men make their way onto the jet, but it has trouble taking off after so long in the cold. Jean decides to use her new powers to get it started while also holding the flood back long enough for the escape, but this forces her to sacrifice herself outside.
The President starts to make an address about the brief crippling pain experienced by all humans, when Xavier mentally contacts him and presents him with evidence that Stryker was behind the whole thing, then leaves him to do what he will with the information. Back at the school, he says hes sure everything will be fine, while back at Alkali Lake a strange bird-shaped glow approaches Jeans body.