The evil demon Aku (Samurai Jack) has created the "League of Extraordinary Villains", composed by malevolent villains from different universes of Cartoon Network. When his evil robots begin to make an appearance in different worlds, heroes from The Powerpuff Girls, Ben 10, Dexter's Laboratory, Ed, Edd and Eddy and Samurai Jack team up to stop the evil plan of the "League of Extraordinary Villains".