Apocalypse has begun his war on humans and mutants, beginning with his invasion of the mutant-controlled nation of Genosha. Professor X and Magneto come to the realization that the only way to defeat this enemy that threatens all life on the planet is for their respective groups to join forces. The story begins with the X-Men and the Brotherhood launching a rescue mission to save Professor X, who has been captured by Apocalypse.
In the following missions, the unlikely group encounter many dangers in Genosha, the Savage Land, Canada's Weapon X Facility, a bombed-out New York City with sewers crawling with Morlocks, and finally, Apocalypse's stronghold in Egypt. Apocalypse is searching for four mutants with "harmonic DNA" to take over the world. Apparently, Polaris, Quicksilver, Emma Frost, and Sabretooth fit the profile, and one by one, they are taken prisoner by Apocalypse, as are Beast & Angel. Things get worse when Destiny forsees a great treachery by one of the X-Men. In the end, the X-Men and Brotherhood have a massive showdown against Apocalypse and his Horsemen. Apocalypse's machine that will help him with his plans eventually malfunctions and the power of the X-Men and Brotherhood push Apocalypse in, trapping him there forever. Apocalypse's Four Horsemen are released from their hypnotization and the world is saved once more with the X-Men and Brotherhood back as enemies again. On the top of an Egyptian pyramid, Apocalypse's assistant, Mr. Sinister, is seen laughing maniacally.