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The game's single-player story mode takes place in the world of Yoshi's Island, where Bowser and his minions have cursed all of Yoshi's friends. Playing as Yoshi, the player must defeat each of his friends in order to remove the curse. Once all friends have been freed, the game proceeds to a series of Bowser's minions, and then to Bowser himself. During these final matches, the player can select Yoshi or any of his friends to play out the stage.

In Block Attack, the player is presented with a playfield consisting of a virtual grid of squares, each of which can be occupied by a colored block. Blocks are stacked on top of one another and rise steadily toward the top of the playfield, with new blocks being added at the bottom. The player must arrange blocks in horizontal or vertical lines of three or more matching colors by swapping blocks horizontally two at a time. As matching lines are formed, the blocks are cleared from the screen and any blocks above them fall into the gaps. The game is over when the blocks touch the top of the playfield, or another game-ending condition is met (such as reaching a time limit or clearing blocks below a set line).

Clearing more than three tiles in a single move scores a Combo, while Chains are scored when falling blocks from one clear cause another clear to occur. Both of these events score extra bonus points, and in multiplayer Versus games, these also send "garbage blocks" to the other player's playfield.