In a secret underwater base, the evil Madame Q is determined to control the world. To that end she has kidnapped thousands of beautiful girls to use in her diabolical experiments. Players are part of a team of experts hired by the government to find and penetrate Madame Q's fortress and free the hostages. After the submarine reaches its destination, players scuba dive to get to the base and must avoid mines and chemical spills as well as battle sharks and enemy divers with their spear-shooting harpoons.

The inside of the fortress is very similar to the territory in Rolling Thunder, and because of this ThunderJaws is considered by many as the unofficial sequel to that game. Levels get progressively harder, more elaborate and contain more enemies as the game progresses. Additional weapons are obtained when dropped by fallen enemies.