Terminator 3: Rise of the Machines is based on the movie of the same name, but with an extended story line. In 2032, the player is the T-850 model 101 Terminator, operating under Skynet control. He is captured and reprogrammed by Kate Brewster to help the human resistance, in addition to being ordered to cross the destroyed battlefields of Los Angeles and Hollywood and take over the Skynet base. Once the base is under their control, Brewster sends the Terminator back in time to protect her younger self and John Connor from the T-X, the technologically advanced female Terminator and Skynet's most lethal killing machine. The Terminator teams up with John and Kate in the present day on their mission to stop Skynet from starting World War III.

The game is a first-person shooter combined with hand to hand combat. The first-person mode features the Terminator Point of View (POV), showing the infrared heads-up information display seen in the movies.