ToeJam & Earl takes place from a top-down perspective in a 2D game world. Its gameplay mechanics were inspired by Rogue, which has led to its description as a Roguelike or dungeon-crawl game. The game contains both single-player and two-player cooperative modes. The latter displays a single screen when both characters are near each other, but splits it apart when they are not. Playing the game with two players reveals dialogue and jokes between the characters not heard in the single player game.
The game is set on Earth, which is represented by randomly generated islands that float in space, each one a layer above the last. They are connected by elevators. Some islands contain pieces of spacecraft wreckage, of which the player must collect 10 to win the game.