No One Can Stop Mr. Domino is a puzzle-based action game with a dash of strategy thrown in for good measure. Taking on the role of either Mr. or Miss Domino (cosmetic differences aside, they're exactly the same), players waddle their way through six timed stages set within suburbia, dropping dominoes while moving along. Each stage is structured within a closed loop, requiring players to first drop dominoes and then knock into them on subsequent laps, with the ultimate goal of hitting certain objects or triggering specific switches. The screen scrolls continuously, requiring players to quickly decide how to complete their task.