Cholla Springs is mostly based on the Sonoran Desert of southwestern Arizona near Phoenix and Tuscon. It is the central region of the territory and borders the regions of Gaptooth Ridge to the west, the Redemption Mountains to the north, Río Bravo to the south, and Hennigan's Stead to the east. A small portion of the South-Eastern border is defined by the San Luis River.
The area is largely desert with saguaro cactus and desert scrub. Most of the land is too arid and dry for farming, making cattle ranching a more preferable choice. Criminals and gangs roam freely across the region, meaning that getting lost can lead to dire consequences. The region consists of wide open desert plains and low lying hills with small rocky canyons and cliffs with jagged peaks. Trees are few and far between, with the largest source of water in the region being Lake Don Julio.
This is the region where the player first begins the game following the journey in the opening cinematic.