The Little Tennessee River is a 135-mile (217 km) tributary of the Tennessee River that flows through the Blue Ridge Mountains from Georgia, into North Carolina, and then into Tennessee, in the southeastern United States. It drains portions of three national forests— Chattahoochee, Nantahala, and Cherokee— and provides the southwestern boundary of the Great Smoky Mountains National Park.

The Tennessee River is the largest tributary of the Ohio River. It is approximately 652 miles (1,049 km) long and is located in the southeastern United States in the Tennessee Valley. The river was once popularly known as the Cherokee River, among other names, as the Cherokee people had their homelands along its banks, especially in what are now East Tennessee and northern Alabama. Additionally, its tributary, the Little Tennessee River, flows into it from Western North Carolina and northeastern Georgia, where the river also was bordered by numerous Cherokee towns. Its current name is derived from the Cherokee town, Tanasi, which was located on the Tennessee side of the Appalachian Mountains.