Something has gone seriously wrong in Klayman's homeland -- Klogg, an evil megalomaniac, wants to destroy the land and basically rule over anything and everyone. Because the task can get difficult at times, he has enlisted the service of fearsome ape-like creatures, Skullmonkeys, to aid in the destruction of planet Idznak. Needless to say, it is up to the player to stop Klogg and his devious plans.

Much like The Neverhood, Skullmonkeys is a 2D platformer built entirely of Claymation characters, enemies, and environments. Throughout the game's seven worlds spanning ninety levels, the basic objective of each is to destroy as many Skullmonkeys as possible. Destroying the simians can be done one of two ways: firing projectile weapons or butt-bouncing off their heads.