The game uses a side-scrolling perspective. Players advance through stages, defeat waves of Foot Clan soldiers and mutants, avoid hazards, and defeat a boss at the end of most stages.

Each turtle has different reach and speed characteristics. Players can walk, jump, attack, throw enemies, and use a special move that consumes health. The arcade version supports cooperative play, and progress follows a fixed sequence of time-themed stages with occasional branching choices.

Use attacks that control groups rather than repeatedly striking one enemy. Throwing Foot soldiers can damage nearby enemies and create space.

Save the special attack for crowded situations or difficult bosses, since it costs health. Learn each stage's hazards and keep moving when enemies surround the turtles.

For cooperative play, spread across the screen without separating so far that one player is overwhelmed. Donatello's reach is useful for safer attacks, while Raphael and Michelangelo are effective at close range.