As Dr. Wily launches an attack on Kennedy Airport in New York, Mega Man suffers damage, whereupon the latter recalls the day he was created by Dr. Light, who used to work with Dr. Wily.
Using a device that enables him to control machines, Dr. Wily seeks to hold the reins of the city, yet Mega Man sets out to thwart his evil scheme.
Mega Man is led to believe that Dr. Wily is going to turn him into a human, while Wily is actually deceiving him in order to control his mind.
As Dr. Wily threatens the city with a machine he invented which creates earthquakes, Mega Man sets out to locate this machine; meanwhile, Dr. Light tries to figure out how to neutralize the earthquakes.
With a mysterious devolution acid falling over Robosaur Park, Dr. Wily has his robots vaccinated against its harmful effect, while Dr. Light strives to find a way to make it stop.
As Dr. Wily seeks to assume control of a hazardous device on the moon in order to use it for destruction, Mega Man follows him there.
After Dr. Wily launches an attack on a mining site underwater, he tries to trap Dr. Light and Mega Man inside a mobile prison by tricking them into thinking that it's a laboratory.
Using mysterious gems that he stole from a museum, Dr. Wily creates a dangerous device that allows him to shrink cities. He also shrinks both Mega Man and Rush.
Owing to an evil invention of Dr. Wily's, Mega Man finds himself in Snake Man's body, whereupon he tries to get acclimatized to it as he goes about saving the world.
As Dr. Wily tries to carry out his evil scheme to freeze cities and substitute their rulers with his own robots, Ice Man decides to mutiny, thinking that Wily favors Air Man over him.
As a band called Cold Steel, which turns out to be Dr. Wily's robots, releases a song that puts people in a trance, only a few remain immune to its effect, including Mega Man.
When Mega Man is sent to the future through the time machine Dr. Light created, he finds out that, since he wasn't around, Dr. Wily managed to gain control of the world, whereupon he sets out to remedy the situation.
After a glitch in Dr. Wily's latest invention causes him and his robots to get stuck on an island with Dr. Light, Mega Man, and Roll, he is forced to cooperate with them to find a way out.