The Big South Fork begins in Tennessee at the confluence of the New River and the Clear Fork River at the southern end of the Big South Fork National Recreation Area near an oil field developed by petroleum interests. It is downstream from extensive coal deposits. This confluence occurs approximately four miles (six km) line distance northwest of the U.S. Highway 27 bridge over the New River, in Scott County, Tennessee. From here, the river runs roughly north. This area is extremely remote. The river flows through a deep gorge which has been eroded through sandstone of the Pennsylvanian Period. A large island, unsurprisingly called "Big Island", is located fairly near the Kentucky state line. Many rapids features have names by which they are well known in the whitewater community. The stream enters McCreary County, Kentucky shortly below this point.
This area was depopulated when the National River and Recreation Area was formed. The balance of the stream course prior to its confluence with the Cumberland River downstream of the National Recreation Area is in Daniel Boone National Forest. It is bridged by Kentucky Highway 92 near the community of Hilltop.