Animaniacs uses a side-view perspective. Players guide the Warner siblings through horizontally scrolling stages, collect or recover movie reels, avoid hazards, defeat enemies, and reach the end of each scenario.

The levels parody different film genres and locations, giving the game a changing visual setting while retaining the same core platforming structure. Yakko, Wakko, and Dot can be used as a group, with character-specific abilities helping the player deal with obstacles and enemies. Progression is stage-based rather than experience-based, and success comes from completing objectives and advancing through the sequence of movie sets.

Learn which Warner sibling is most useful for each obstacle before rushing through a stage. Explore side paths for useful items, but avoid unnecessary damage when the route forward is clear.

Use a steady pace around moving hazards and enemies. Because the game is stage-based, memorizing troublesome sections and approaching them with the right character is usually more effective than repeatedly attacking.