The Tombigbee River is a tributary of the Mobile River, approximately 200 mi (325 km) long, in the U.S. states of Mississippi and Alabama. Together with the Alabama, it merges to form the short Mobile River before the latter empties into Mobile Bay on the Gulf of Mexico. The Tombigbee watershed encompasses much of the rural coastal plain of western Alabama and northeastern Mississippi, flowing generally southward. The river provides one of the principal routes of commercial navigation in the southern United States, as it is navigable along much of its length through locks and connected in its upper reaches to the Tennessee River via the Tennessee-Tombigbee Waterway.

The Mobile River is located in southern Alabama in the United States. Formed out of the confluence of the Tombigbee and Alabama rivers, the approximately 45-mile-long (72 km) river drains an area of 44,000 square miles (110,000 km2) of Alabama, with a watershed extending into Mississippi, Georgia, and Tennessee. Its drainage basin is the fourth-largest of primary stream drainage basins entirely in the United States. The river has historically provided the principal navigational access for Alabama. Since construction of the Tennessee-Tombigbee Waterway, it also provides an alternative route into the Ohio River watershed.