After Megamind causes an accident that makes Mr. Donut lose his memory, he convinces himself that the loveable shop owner is on the verge of turning evil and vows to stop him before he becomes a supervillain.

When Chum accidentally sprays a roach with an experimental intelligence substance that causes it to become a super genius, Megamind, Keiko and Chum must get rid of the spray and contain the roaches before they take over the city.