The game is set in the fictional state of San Andreas, which contains three metropolitan cities: Los Santos, based on Los Angeles, San Fierro, based on San Francisco and Las Venturas, based on Las Vegas. Set in late 1992, San Andreas revolves around the gang member Carl "CJ" Johnson returning home from Liberty City to Los Santos, San Andreas, after learning of his mother's murder. CJ finds his old friends and family in disarray. Over the course of the game, CJ gradually unravels the plot behind his mother's murder.
The high-level plot strongly resembles the LAPD Rampart Scandal and the game even culminates with a spoof of the 1992 Los Angeles riots.
San Andreas is structured similarly to the previous two games in the series. The core gameplay consists of elements of a third-person shooter and a driving game, affording the player a large, open world environment in which to move around. On foot, the player's character is capable of walking, eating, running, sprinting, swimming, climbing (the first GTA game in which swimming and climbing is possible) and jumping as well as using weapons and various forms of hand to hand combat. Players can drive a variety of vehicles, including automobiles, buses, semis, boats, fixed wing aircraft, helicopters, trains, tanks, motorcycles and bikes. Players may also import vehicles rather than steal them.
The open, non-linear environment allows players 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, they are not required as players can complete them at their own leisure. When not taking on a storyline mission, players can free-roam and look around the cities, eat from the restaurant, 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 people, pointing guns at people, stealing cars, killing a few people, etc.), whereas SWAT teams, the FBI, and the military respond to higher wanted levels.
The player can partake in a variety of optional side missions that can boost their character's attributes or provide another source of income. The traditional side missions of the past 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. New additions include burglary missions, pimping missions, truck and train driving missions requiring players to make deliveries on time, and driving/flying/boating/biking schools, which help players learn skills and techniques to use in their corresponding vehicles.
Not all locations are open to the player at the start of the game. Some locales, such as pay 'n spray, gyms, and shops, become available only after completing certain missions. 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 certain missions.
Unlike GTA III and Vice City, which needed loading screens when traveling between different districts of the city, San Andreas has no load times when the player is in transit. The only loading screens in the game are for cut-scenes and interiors. Other differences between San Andreas and its predecessors include the switch from single-player to multiplayer Rampage missions (albeit not in the PC version), and the replacement of the 'hidden packages' with spray paint tags, hidden camera shots, horseshoes, and oysters to discover.
The camera, fighting, and targeting controls were reworked to incorporate concepts from another Rockstar game, Manhunt, including various stealth elements, as well as improved target crosshairs and a target health indicator which changes colors from green to red to black depending on the target's health. The PC version of the game implements mouse chording; the player has to hold the right mouse button to activate the crosshairs, and then click or hold at the left mouse button to shoot or use an item, such as a camera. The player has a gunfight with members of an enemy gang.
In addition, players can swim and climb walls for the first time in the series. The ability to swim has a great effect on the player as well, since water is no longer an impassable barrier that kills the player (although it is possible to drown). For greater firepower, players can also wield dual firearms or perform a drive-by shooting with multiple gang members. Due to the size of San Andreas, a waypoint reticule on the HUD map can be set, aiding the player in reaching a destination.