- Halle Berry as Ororo Munroe / Storm: A Kenyan teacher at the X-Mansion who has become bitter with other people's hatred for mutants, and while comforting a dying Senator Kelly says that she sometimes hates humans, but mostly because she is afraid of them. Her mutant powers include weather manipulation.
- Famke Janssen as Dr. Jean Grey: The doctor of the X-Mansion who has a romantic relationship with Cyclops. Her mutant powers include telekinesis and telepathy that are similar to but much less advanced than that of Xavier's, as displayed when she is stunned by the usage of Cerebro.
- Anna Paquin as Marie / Rogue: A seventeen-year-old girl forced to leave her home in Mississippi when she puts her boyfriend into a coma by kissing him. Her mutant powers include absorbing anyone's memories, life force, and, in the case of mutants, powers through physical touch.
- James Marsden as Scott Summers / Cyclops: Xavier's second-in-command and the X-Men's field leader, as well as an instructor at the Institute. He is in love with Jean Grey and has a relationship with her. His mutant powers include a strong red beam of force shooting from his eyes, which is only held in check by sunglasses or a specialized ruby-quartz visor, which also enables him to control the strength of the beam to fire when in combat.
- Rebecca Romijn-Stamos as Raven Darkhölme / Mystique: Magneto's loyal second-in-command, who seems completely facile with respect to modern technology. Her mutant powers include altering her shape and mimicking any human being, which is almost secondary to her role as "the perfect soldier".