
Unlike Grand Theft Auto III and Vice City, which needed loading screens when the player moved between different districts of the city, San Andreas has no load times when the player is in transit. If the player travels to locked locations early in the game, they will attract the attention of SWAT teams, police, and police-controlled Hydras if in an aircraft.

Likewise, for the first portion of the game, only Los Santos and its immediate suburbs are available for exploration unlocking the other cities and rural areas again requires the completion of specific missions. Some locales, such as mod garages, restaurants, gyms, and shops, become available only after completing specific missions. Not all locations are open to the player at the start of the game. New additions include burglary missions, pimping missions, truck and train driving missions requiring the player to make deliveries on time, and driving/flying/boating/biking schools, which help the player learn skills and techniques to use in their corresponding vehicles. The traditional side missions of past Grand Theft Auto games are included, such as dropping off taxi cab passengers, putting out fires, driving injured people to the hospital, and fighting crime as a vigilante. The player can partake in a variety of optional side missions that can boost their character's attributes or provide other sources of income.

The more chaos caused, the stronger the response: police will handle "minor" infractions (attacking pedestrians, pointing guns at people, stealing vehicles, manslaughter, etc.), whereas SWAT teams, the FBI, and the military respond to higher wanted levels. Creating havoc can attract unwanted and potentially fatal attention from the authorities. 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. Although storyline missions are necessary to progress through the game and unlock certain cities and content, the player can complete them at their leisure. The open, non-linear environment allows the player to explore and choose how they wish to play the game.

The player may also import vehicles in addition to stealing them. The player can operate a variety of vehicles, including automobiles, buses, semis, boats, fixed-wing aircraft, helicopters, trains, tanks, motorcycles, and bicycles. 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. 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.

Grand Theft Auto: San Andreas is an action-adventure game with role-playing and stealth elements.
