Big Mutha Truckers is primarily a racing game, in the same vein as 18 Wheeler: American Pro Trucker. Players spend the majority of their time on the road, navigating the highways between the game's six cities: Salt Sea City, Capital City, Greenback, Skeeter's Creek, Smokestack Heights, and Big Mutha Truckin' Incorporated. The player will earn most of their money through trade, shipping goods from cell phones to beer, with additional opportunities from mini-games and challenge races.
Every city features three locations: a garage, a bar, and a store. The garage allowed players to repair damage, refuel, switch trailers to carry different kinds of cargo, buy upgrades to improve their rig, or design custom logos for their truck. In the bar the player can find tips on where to buy and sell certain cargo, and a loan shark. The store allows the player to buy and sell goods, with prices varying by town. When visiting Big Mutha Truckin' Incorporated, the bar and store are replaced by visits to Ma Jackson.