Grand Theft Auto: San Andreas is an action-adventure game with role-playing and stealth elements. Structured similarly to the previous two games in the series, the core gameplay consists of elements of third-person shooter and driving games, affording the player a large, open world environment in which to move around. On foot, the player's character is capable of walking, running, sprinting, swimming, climbing, and jumping as well as using weapons and various forms of hand-to-hand combat. The player can operate a variety of vehicles, including automobiles, buses, semis, boats, fixed-wing aircraft, helicopters, trains, tanks, motorcycles, and bicycles. The player may import vehicles in addition to stealing them.

The open, non-linear environment allows the player to explore and choose how they wish to play the game. Although storyline missions are necessary to progress through the game and unlock certain cities and content, the player can complete them at their leisure. When not taking on a storyline mission, the player can freely roam the cities and rural areas of San Andreas, eat in restaurants, or cause havoc by attacking people and causing destruction. Creating havoc can attract unwanted and potentially fatal attention from the authorities. The more chaos caused, the stronger the response: police will handle "minor" infractions (attacking pedestrians, pointing firearms at people, stealing vehicles, manslaughter, etc.), whereas SWAT teams, the FBI, and the military respond to higher wanted levels.