Known as Hershberger Road, the state highway runs 3.17 miles (5.10 km) from SR 117 east to U.S. Route 11 (US 11) within Roanoke.

SR 101 is a major east–west arterial on the north side of Roanoke, where it connects Interstate 581 (I-581) and US 220 with Roanoke–Blacksburg Regional Airport.

The state highway heads east as a two-lane undivided road between the Westview Terrace and Washington Heights neighborhoods.

SR 101 passes along the southern edge of the Roanoke Regional Airport property and has a partial cloverleaf interchange with the intersecting boulevard, which heads south as Valley View Boulevard toward the Valley View Mall and north as Aviation Drive to provide access to the airport.

The state highway continues east through another commercial area to its eastern terminus at US 11 (Williamson Road).