In Meridian, Mississippi, 17-year-old Marie D'Ancanto accidentally puts her boyfriend into a coma upon kissing him which was caused by her unknown superhuman ability to absorb the life force and mutant abilities of anyone she touches. In fear that she is harmful, Marie, now going by the name of Rogue, runs away to Laughlin City, Alberta. While at a bar, she meets Logan, an amateur fighter known as "Wolverine", who also possesses superhuman healing abilities, heightened senses, and metal claws that extend outwards from between his knuckles. While on the road together, both of them are attacked by Sabretooth, a fellow mutant and an associate of Magneto. Cyclops and Storm arrive and save Wolverine and Rogue, and bring them to the X-Mansion in Westchester County, New York. They are introduced to Xavier, who leads a group of mutants called the X-Men, who are trying to seek peace with the human race, educate young mutants in the responsible use of their powers, and stop Magneto from starting a war with humanity.
Senator Kelly is abducted by Magneto's allies Toad and the shapeshifter Mystique and brought to their lair. Magneto uses Kelly as test subject of a machine that artificially induces mutation. Kelly uses his new mutant abilities to escape imprisonment. After an accident causes Rogue to use her powers on Wolverine, she is convinced by Mystique (disguised as classmate Bobby Drake) that Xavier is angry with her and that she should leave the school. Xavier uses his mutant-locating machine Cerebro to find Rogue at a train station. Mystique infiltrates Cerebro and sabotages the machine.
At the train station, Wolverine convinces Rogue to stay with Xavier, but a fight ensues when Magneto, Toad and Sabretooth arrive to take Rogue. Kelly arrives at Xavier's school, shortly before dying due to the instability of his artificial mutation. The X-Men learn that Magneto was severely weakened in the test of the machine on Kelly, and realize that he intends to use Rogue's power-transferring ability so that she can power the machine in his place, putting her life at risk. Xavier attempts to use Cerebro to locate Rogue, but Mystique's sabotage causes him to fall into a coma. Fellow telepath Jean Grey fixes and uses Cerebro, learning that Magneto plans to place his mutation-inducing machine on Liberty Island and use it to mutate the world leaders meeting for a summit on nearby Ellis Island.
The X-Men scale the Statue of Liberty, defeating Toad and incapacitating Mystique, before Magneto and Sabretooth incapacitate the group and continue with their plans. Magneto transfers his powers to Rogue, forcing her to use them to start the machine. Wolverine escapes and defeats Sabretooth. Storm uses her weather-controlling powers and Jean her telekinesis to lift Wolverine to the top of Magneto's machine. Wolverine saves Rogue, with Cyclops knocks out Magneto, and destroys the machine. Wolverine touches the dying Rogue's face, and his regenerative abilities are transferred to her, causing her to recover.
Professor Xavier recovers from his coma. The group learns that Mystique is still alive, and impersonating Senator Kelly. Xavier tells Wolverine that near where he was found in Canada is an abandoned military base that might contain information about his past. Xavier visits Magneto in a prison cell constructed entirely of plastic, and the two play chess (Xavier seems to have the upper hand). Magneto warns that he will continue his fight, to which Xavier promises that he and the X-Men will always be there to stop him. As Xavier is being taken away from the prison by a guard, Magneto pushes his king chess piece over.