The X-Men and the Brotherhood of Mutants, old enemies by instinct, agree to a temporary alliance to free Professor X and Polaris from a military prison in Greenland. After the rescue, they relocate to Genosha, which has been devastated by Apocalypse's forces. Mister Sinister is there too, using Genoshan mutants as experimental subjects. Quicksilver has been captured; Beast is taken from the X-Mansion shortly after.
The trail leads to the Savage Land, then to New York City, where the Syndicate's operations are expanding and both Deadpool and Angel have been captured or compromised. Angel is forcibly transformed into Archangel, a Horseman of Apocalypse, before the heroes can reach him.
In Egypt, the full scope of Apocalypse's plan becomes clear: four mutants with Harmonic DNA — Polaris, Quicksilver, Emma Frost, and Sabretooth — are to be fed into a machine that will grant him overwhelming power. The heroes defeat Mister Sinister, free Beast from his control, and destroy the machine by stealing the power from it. In the aftermath, Sinister is glimpsed on top of the pyramid — laughing.