Like its predecessor, Mega Man: Dr. Wily's Revenge, Mega Man II reuses content from the NES games, both graphics and actual level construction. The first four available Robot Masters are from Mega Man 2, while the last four are taken from Mega Man 3. The game also introduces many of Mega Man 3's features to the Game Boy series. Mega Man is able to slide. Rush also appears for the first time in the Game Boy series, allowing the use of the Rush Coil, Rush Marine, and Rush Jet. The game also features full stages for the last four Robot Masters, rather than single-room boss fights as in Mega Man: Dr. Wily's Revenge. However, these stages are still accessed via Wily Teleporters, rather than a traditional stage select screen, and special weapon energy does not recharge between these stages.
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.
Dr. Wily having finally managed to modify the time machine, discovers that the time machine could now only travel into the future and back, not into the past. Dr. Wily modified his plan and decided instead to spy on Mega Man’s future. Travelling approximately 37.426 years into the future (as stated in the American manual), Wily found that the future was peaceful, as his future self had reformed and Mega Man no longer needing weapons, had been reset back into a peaceful household robot. Recognizing this chance, Wily convinces his future self to abduct the now defenseless Mega Man. Dr. Wily then proceeds to capture Mega Man, and modifies him into the fighting robot Quint, reprogramming him to make him fight against the Mega Man of the present.
Back in the present time, Mega Man and Rush were finally closing in on Wily’s fortress, defeating the first four once again revived set of Robot Masters. After penetrating into Wily's lair, Mega Man finds another four Robot Masters awaiting him via teleporters. Mega Man manages to defeat all eight of his adversaries and engages his modified future self Quint in combat. After defeating him, Mega Man obtains his weapon, a pogostick-like device called the Sakugarne. With it, he makes his way to Wily's space fortress and defeats him yet again.
The sound effect when the player picks up an extra life is very reminiscent of the coin pick-up sound from the Super Mario Bros. series.
This is the only Mega Man classic Game Boy game to use Rush Marine.
Mega Man II is one of the few Game Boy titles that does not reset with the Game Boy's "A+B+Start+Select" reset configuration.
After Dr. Wily is defeated, Mega Man obtains the missile attack Dr. Wily used in the final battle. Mega Man uses it when he destroys Dr. Wily in the final cutscene.
Keiji Inafune considers this to be his least favorite of the Game Boy series of Mega Man games, due to the fact that the game was outsourced to a different company than the one that worked on Mega Man: Dr. Wily's Revenge, with this new company being unfamiliar with Mega Man. Inafune would return to the company that worked on Dr. Wily's Revenge for the rest of the Game Boy series of games.