In the fictional country of Eagleland sometime in the 1990s, a young boy named Ness investigates a meteorite crash with his neighbor Pokey and discovers that an alien force called Giygas has saturated the world in hatred, corrupting animals, people, and objects into hostile creatures. A small, beetle-like creature from the future called Buzz-Buzz tasks Ness with collecting eight melodies from sanctuaries across the land to stop Giygas before he can complete his work — then is killed almost immediately. Ness travels through cultist villages, zombie-infested towns, alien-controlled cities, desert ruins, deep swamps, and the interior of his own subconscious before his friends — Paula, Jeff, and Poo — are finally assembled and the group is ready to fight Giygas directly. They travel back in time, transfer their souls into robot bodies to survive the journey, and confront Giygas at his most powerful and least comprehensible. The prayers of every person Paula and Ness have ever met — and eventually the player's own — are what finally bring the alien down.