Known as the Trail of the Lonesome Pine, the state highway runs 8.02 miles (12.91 km) from the Kentucky state line on top of Black Mountain, where the highway continues north as Kentucky Route 160 (KY 160), east to SR 68 in Appalachia.

Due to the mountainous terrain and numerous tight bends, Virginia State Route 160 and its Kentucky State Route 160 counterpart are signposted closed to tractor-trailers between Lynch, KY and Appalachia, VA. SR 160 begins on top of Black Mountain at the Kentucky state line, which follows the Tennessee Valley Divide.

SR 160 has a winding descent featuring several hairpin turn to the valley of Looney Creek, which the highway follows east toward Appalachia.

The state highway enters the town shortly before reaching its eastern terminus at its intersection with SR 68 (Exeter Road), which itself reaches its terminus at U.S. Route 23 Business (Main Street) at the southern edge of downtown Appalachia.

For a few years in the early 1930s, SR 106 carried U.S. Route 23 from Appalachia to Kentucky, but US 23 was soon realigned to its current route; the piece of SR 106 south of Big Stone Gap continued to carry US 23 and was thus eliminated in 1933.