The Simpsons: Road Rage is similar to Sega's 1999 video game Crazy Taxi, in that the main objective is to drive picked up passengers to their destinations as quickly as possible. The player receives money upon successfully dropping off each passenger, and bonuses are obtained when they are transported in a short amount of time. Players have to avoid certain hurdles, such as other vehicles and Burns' nuclear transit buses.

The game contains sixteen different collectible vehicles, six starting locations, and ten different missions. In order to collect the vehicles and unlock starting locations, players must earn progressively more money for each vehicle or starting location they want to get.

Mr Burns has taken over Springfield's transit company and replaced the buses with nuclear powered buses; not only that but they also cost a lot to ride. But the people of Springfield won't accept this and decide to try to take back the transit company from the evil corporate hands of C. Montgomery Burns.