The bi-state highway begins at an intersection with NY 22 in the hamlet of North Petersburgh and heads generally southeastward across the New York–Vermont state line to a junction with U.S. Route 7 (US 7) in the village of Pownal.

VT 346, the longer of the two routes at 4.628 miles (7.448 km) in length, is currently the highest-numbered state highway in Vermont.

The switch in positioning is made just east of the state line, where VT 346 crosses over the waterway.

The route continues eastward, intersecting Indian Massacre Road, the continuation of CR 96, and crossing a Pan Am Railways-owned railroad line on its way to a junction with Lime Kiln Road, a local highway leading to the village of Pownal Center.

The route heads generally north–south through the community, running alongside both the Hoosic River and the Pan Am Railways line.