The New River rises on Frozen Head, a notable mountain of Morgan County, Tennessee named for its frequent winter appearance and the focal point of a Tennessee State Park and Natural Area. Draining an area of Pennsylvanian Period rock that has been subjected to extensive strip mining for coal, the upper reaches of the stream have at times been subject to heavy pollution. The stream initially trends northeast. The upper portion of the course is paralled by Tennessee Highway 116. It soon crosses into a remote area of Anderson County, and then into Campbell County. At this juncture, Tennessee Highway 116 turns to the southeast, and the road paralleling the New River becomes a small county road. The stream trends generally north from this point for several miles, and is also paralleled by a railroad constructed primarily for the purposes of coal transport.

The stream, road, and railroad cross into Scott County. Several miles into Scott County, the stream begins a westerly trend. It drains an area developed by the petroleum industry as an oil field, and is crossed by U.S. Highway 27 at the community of New River. Just downstream of this commuity is the boundary of the Big South Fork National Recreation Area. The New River is joined slightly downstream of this point by the Clear Fork River and the stream downstream from this point is known as the Big South Fork of the Cumberland River.