A year after the events in Mega Man Zero, the hero finds himself in another battle to save the world. Caught in-between the reploids and humans, Neo Arcadia's new commander has tricked Zero into helping her, although her reasons are uncertain.

To fix the problem, Zero must battle through level after level, using the new Chain Rod weapon to grapple onto ledges to gain an advantage in collecting out of reach items or attacking enemies from above. Cyber Elfs can again be collected to gain some helpful powerups.

New to the series is a two player challenge mode, where the first to complete the level wins.