As the world progresses into the industrial age, a professor studying the "nature of pure matter" is spirited away by a would-be dictator and connived into building a super-bomb, as a young reporter and a girl rescued from the sea attempt to warn him of their mutual kidnapper's intentions to dominate the world with a new and more-deadly-yet weapon.

For their first day on the job as the new protectors of Metro City, Megamind and Minion are selling off the gadgets from their evil lair. But when one seemingly harmless "button" unleashes the gigantic robot MEGA-MEGAmind, the duo will have to resort to their old tricks to restore order.