The movie license Lethal Weapon on the SNES is broadly similar to the game on computers, but features unique levels and different gameplay mechanics.

Playing as either Riggs (who has a faster rate of fire) or Murtaugh (who can jump higher), the player selects a mission from police headquarters. The first four missions can be tackled in any order before the final mission opens up. Each mission consists of a large number of interconnected levels consisting of ladders and platforms, which must be navigated to the mission goal, all within a tight time limit. Featured locations are the docks, the sewers and subway, a shopping mall, an office complex, and a police station.

Many enemy goons stand in the player's way and can be dispatched via karate kicks or gunshots. Ammunition is limited and clips must be collected to keep up the supply. Also available are bullet-proof vests functioning as health power-ups as well as clocks, which add one minute to the time limit. Most missions end with boss fights.