The state highway runs 35.22 miles (56.68 km) from U.S. Route 29 (US 29) at Buffalo Hill north to US 250 at Critzers Shop.

SR 151 traverses the Blue Ridge foothills of western Nelson County, where the highway provides access to the Wintergreen Resort.

SR 151 passes through the village of Clifford, which contains the historic homes Brick House and Winton; the latter property is preserved as part of a country club.

The state highway curves around Turkey Mountain and enters Nelson County by crossing the Piney River.

At SR 664 (Beech Grove Road), the primary access highway to the four-season Wintergreen Resort, SR 151's name changes to Rockfish Valley Road, which follows the South Fork of the Rockfish River past the Devil's Backbone Brewing Company brewpub and the historic home River Bluff.