It's your mission to help the exiled scientist Ciel discover the source of a new reploid energy! Play as Mega Man's pal Zero, the reploid from the Mega Man X series turned good by the infectious Sigma Virus and 100 years of sleep. Conquer your adversaries and find the energy source... or risk ultimate defeat. It's up to you to defend good from the destructive powers in the universe.

Over a century after Sigma's defeat in the Mega Man X series, a new government called Neo Arcadia was formed to maintain peace. The leaders of Neo Arcadia began hunting down Reploids unjustly labeling them as Mavericks. Now the only hope for the Reploid is a legendary Reploid: the Red Hero that is named Zero. Feeling that the Reploids were being wrongly accused, Ciel flees from Neo Arcadia and creates a Resistance against Neo Arcadia.

The game begins as Ciel and a small group of resistance soldiers is being hunted by Pantheons and Golems. Some of the resistance soldiers fall behind, but they can't stop their advance. Pursued, Ciel reaches a huge door. Passy, her Cyber-elf says: "I feel strong energy emanating from here. This must be the place." After that, soldiers blow up the door, and Ciel, Passy and Milan enter the room, with Zero's lifeless body in the middle of room, inactive for 100 years. Milan tries to touch it, but he is knocked back by energy shield that protects Zero. While they try to figure out how to bypass the shield, Pantheons appear at the door. Milan orders Ciel to run, and dies, being hit by one of the Pantheons. Passy tells Ciel: "You have to use my power. You have no choice." Ciel thinks while Pantheons come closer and closer, and agrees sadly. Passy's sacrifice breaks the energy shield and brings Zero back to life. He helps Ciel, and learns that Mega Man X (although actually a copy) is the one responsible for innocent Reploids being retired.