Mutants continue their struggle against a society that fears and distrusts them. Their cause becomes even more desperate following an incredible attack by an as yet undetermined assailant possessing extraordinary abilities. The shocking attack renews the political and public outcry for a Mutant Registration Act and an anti-mutant movement now led by William Stryker, a wealthy former Army Commander who is rumored to have experimented on mutants.

Stryker's "mutant" work is somehow tied to Logan's mysterious and forgotten past.  As Wolverine searches for clues to his origin, Stryker puts into motion his anti-mutant program - launching an attack on Xavier's Mansion. Magneto, newly escaped from his plastic prison, proposes a partnership with the X-Men to combat their common and formidable enemy: Stryker. With the fates of Xavier, mankind - and mutantkind - in their hands, the X-Men face their most dangerous mission ever.