Six months pass, and the war against the Mavericks is almost over. Mega Man X has assumed command of the Maverick Hunters, and they are about to crush the Maverick insurection, when they and Dr. Cain are contacted by Agile, Serges, and Violen, the X-Hunters. They have Zero' parts, and intend to resurrect him to fight for the Maverick cause. X, in a desperate attempt to save him, fights through Wire Sponge, Wheel Gator, Bubble Crab, Flame Stag, Morph Moth, Magna Centipede, Crystal Snail, and Overdrive Ostrich, then through the X-Hunters, each making reference to "the prophesy". Sigma is back! Zero is then brough back to life, and Sigma is defeated again. But, this is not the end.
A year passes. All Mavericks have been neutralized, thanks to the efforts, know-how, and neuro-computer of a Reploid scientist named Dr. Doppler. They then settle in a utopian Reploid society called DoppleTown. Little time passes, however, before they begin to go berserk and riot after becoming infected with a strange virus. Dr. Doppler is then implicated as he ringleader, but not before the Reploids storm Maverick Hunter Headquarters. Mega Man X and Zero, now the leader of a special 0-unit, repel the attack and set out to stop the revolt, taking on Blizzard Buffalo, Toxic Seahorse, Tunnel Rhino, Volt Catfish, Crush Crawfish, Neon Tiger, Gravity Beatle, and Blast Hornet with the help of new ride armors, enhancements and now enhancement chips, which enhance the enhancements. He also gets help from Zero, who is useable in certain parts of the game. Doppler sends Bit and Byte, and a new and improved Vile, in the new ride armor "Goliath." Upon defeting Doppler, X finds that Doppler was corrupted by the virus, which is actually Sigma's true form, and that Dopppler has built a new super battle body for his controller to occupy. X destroys the body and, after narrowly escaping being possesed himself, X sees Dr. Doppler die for his attrocities to destroy Sigma and Zero eliminate him with an Anti-Sigma virus program. In the end, it is revealed that in the end, X must destroy Zero to save humanity.
Zero has a startling dream. In it, he stands over human bodies, covered in blood. He is awakened when an alarm sounds. Long after Sigma was annhialated, a new faction of Reploids forms: the Repliforce. Commanded by General and his second-in-command Colonel, they are watched carefully by all. Magma Dragoon, a Maverick Hunter, causes a floating lava bed to come crashing to the ground, causing untold carnage. X, a commander of Unit #14, and Zero commanding his elite Unit #0, are sent to investigate. X is confronted by General and Zero meets with Colonel, who thanks him for rescuing his sister Iris in the catastrophe. Zero, with his Beam Saber, and X, with his X-buster, are then sent to war against the Repliforce, who is held responsible for the fall of the lava bed. The Repliforce takes offense to being branded as a faction of Mavericks, and begins construction of a superweapon to defend themselves and their dream of a Reploids-only nation of their own. Double, a clumsy Maverick Hunter, is assigned to X's unit. Iris accompanies Zero, though she is torn between her love for her brother and her love for him. Operating independantly, X and Zero fight new, powerful Reploids. Magma Dragoon, the traitor to the Maverick Hunters who caused the accident, always wanted to test his mettle against X and Zero. Frost Walrus is an older Reploid with little respect for the two Maverick Hunters. Cyber Peackock launches an assault in Cyberspace. Storm Owl, a dedicated Repliforce leader, becomes furious with them for attacking his air squadron. Slash Beast sees X and Zero as potential prey. Web Spider, a former Maverick Hunter, resents how the Repliforce is regarded. Split Mushroom has orders from an undisclosed party to kill X and Zero. Jet Stingray decimates a human city and is chased down by X and Zero. After fighting all eight, Double is revealed to be a traitor and is defeated by X. Iris sides with her brother, and Zero, very regretfully, must defeat her. She dies in his arms, urging him not to continue. They fight their way through Colonel, and discover that Sigma is alive! He has been manipulating the Repliforce and Maverick Hunters to get a hold of the Repliforce's superweapon. General sacrifices himself to destroy it, and the final battle begins. Sigma reminds Zero that he was once a Maverick, before he saw the light and joined the Hunters. Sigma is defeated once again, but X fears that one day he, too, may go Maverick. He makes Zero promise that if that ever happens, he will destroy X.