Apocalypse (Oscar Isaac), the firstborn of the mutant race, rules the world in ancient Egypt, but is betrayed by his worshippers and entombed for centuries, while his followers, the Four Horsemen, are destroyed.
He is awakened in 1982 to learn that the world has forgotten him. Believing that without his presence humanity has grown weaker, Apocalypse decides to destroy it in order to rebuild society to his image, and sets to recruit four mutants to do his bidding.
His first recruit is Storm (Alexandra Shipp), a kindly pickpocket from Cairo. She worships Mystique (Jennifer Lawrence), who has become a revered figure in the mutant community for saving the President of the United States and ushering a new era of pacific coexistence between humans and mutants.
Mystique is investigating an underground fight club where mutants are forced to battle, and happens upon a fight between the champion, Angel (Ben Hardy), a hardened fighter, and newcomer Nightcrawler (Kodi Smith-McPhee), who gets the upper hand and and electrocutes Angel, leaving him injured. Mystique rescues Nightcrawler, while Apocalypse arrives to cure Angel, who is reborn as Archangel.
In New York City, Cyclops (Tye Sheridan) learns about his powers and is taken by his estranged older brother Havok (Lucas Till) to the Xavier School for Gifted Youngsters to learn how to control them with Professor Charles Xavier (James McAvoy) and Beast (Nicholas Hoult). He is reluctant until he meets Xavier's protege, Jean Grey (Sophie Turner), who is likewise unable to control her powers, and the two develop an attraction.