The Holston River is a major river system of southwestern Virginia and East Tennessee. The three major forks of the Holston rise in southwestern Virginia and have their confluence near Kingsport, Tennessee. From there the river flows roughly southwestward until it reaches its confluence with the French Broad River just east of downtown Knoxville, Tennessee. This confluence is considered to be the headwaters of the Tennessee River.

The Holston River valley is greatly developed for electrical power generation, both with hydroelectric dams and coal-fired steam plants. In its upper reaches some of these plants are controlled by private interests; in the downstream portion they are owned by the United States Government's Tennessee Valley Authority.