The second handheld installment of the Mega Man series has him (along with his dog, Rush) defeating eight more revived Robot Masters (from Mega Man 2 and Mega Man 3), while finding the whereabouts of Dr. Wily (who has traveled into the future to steal a weapon to counter Mega Man).

Even after his crushing defeat at the hands of Mega Man during the events of Mega Man: Dr. Wily's Revenge, Dr. Wily was already planning his next scheme. If he could get his hands on the time machine (named Time Skimmer in the American manual) that was being developed at the Time-Space Research Laboratory (named Chronos Institute in the American manual), he thought he just might be able to change the past.

After stealing the time machine, Wily had wanted to set out immediately on a trip across time, but had to put an emergency brake down on his plans when he discovered that the time machine had a serious flaw.

Meanwhile, Dr. Light had been dispatched to the time-space laboratory to investigate. With the help of Rush’s super-sense of smell, he was able to deduce that it was none other than Dr. Wily behind the theft. Having a bad feeling about the incident, Dr. Light quickly called upon Mega Man and Rush to search out Dr. Wily’s whereabouts.