As in previous games of the franchise The Sims 2, in the Sims 3, players control their own Sims' activities and relationships. The gameplay is open-ended and does not have a defined goal. The Sims live in neighbourhoods, now being officially referred to as 'worlds', which can be customised, allowing players to create their houses, community lots, and sims, although many of these come with the core game.

These worlds are now 'seamless', allowing all sims to move freely without any loading screen between lots, as in previous games. Thus, the neighbourhood includes community lots which can be leisure lots (such as parks, markets, gyms, and movie theatres) and job lots (town hall, hospital, and businesses). Since the neighbourhood is open, the game includes the "Story Progression" mechanic, which allows all Sims in the area to autonomously continue their lives without the player ever controlling them. This helps advance the whole neighbourhood's story instead of only the active playing units. Sims live for a set duration that the player adjusts and goes through several life stages (baby, toddler, child, teen, young adult, adult, and elder). Sims can die of old age or prematurely from causes such as fire, starvation, drowning, and electrocution.

The primary world in the game is Sunset Valley (in the console version, the leading world is Moonlight Bay), while an additional world called Riverview can be obtained for free. All expansion packs (except Generations and Seasons) have included a world, and other worlds can be bought at The Sims 3 Store for SimPoints. Additionally, Sunset Valley and a few of the other planets available have some degree of connection to the storyline set up by The Sims and The Sims 2. In-game Sunset Valley is stated to be the same town as the default neighbourhood in The Sims, and Pleasantview from The Sims 2, although set twenty-five and fifty years earlier, respectively. Several pre-made characters from other Sims games appear throughout the Sims 3's worlds, many of them in younger form.