Mario Andretti Racing follows the story of Mario Andretti, an Italian-born racing driver who has achieved great success in the US scene. He comes from a family of skilled drivers, with five relatives having also competed professionally. Players take on the role of Andretti and his fellow drivers as they compete in various types of cars, including Indy cars, stock cars, and sprint cars.
The gameplay involves racing against 27 computer-controlled cars, each with their own unique characteristics. The physics engine is tailored to each type of car, resulting in distinct handling and behavior on different tracks. Players can choose from 8 cars per race, each with varying engine, grip, brakes, and pit crew abilities. Strategies must be employed during longer races, including the option to use a "splash 'n' dash" stop to maintain speed when tires are still fine.