Main article: Puzzle League § Gameplay
Pokémon Puzzle Challenge features gameplay similar to other games in the Puzzle League series; players control a two square long cursor that can swap or move blocks around the field. The objective is to remove blocks from the player's puzzle grid as new ones appear from the bottom. Placing three or more blocks of the same color in a horizontal or vertical line will cause them to disappear. Players can also perform combos by clearing more than three blocks at once, as well as chains when falling blocks from one clear cause another set of blocks to clear. A game typically ends when the blocks reach the top of the grid, at which point the player loses. In competitive modes, players can perform combos and/or chain clears to cause objects called garbage blocks to fall on their opponent's grid, further filling it in an attempt to cause them to lose. Concessions are made due to the game's limited screen size: Puzzle Challenge features a puzzle grid size of only 6x9 blocks, compared to the 6x12 grids of other Puzzle League games, and the opponent's grid is not visible, with a small meter instead indicating how close they are to losing.