Tom and Jerry in Fists of Furry features 10 levels, each with themes like the kitchen from the Tom and Jerry TV show and a boxing ring. With gameplay based on slapstick comedy, players interact with the environment and scattered usable objects like chairs, pool cues, and bombs. Each of the seven characters have unique attacks. Power-ups include invincibility to items (but not to punches or the stage hazards), or a green gas which can contaminate a touched opponent.

Beside Tom and Jerry, other playable characters from the television series include Butch, Duckling, Tuffy, and Spike and Tyke.