PA 331 begins at the West Virginia state border, at the eastern terminus of WV 67.

The route heads east in Independence Township paralleling Buffalo Creek.

After 1.8 miles (2.9 km), the route makes a left turn onto Mount Hope Ridge Road.

[2] Prior to 2005, PA 331 followed a more direct route between the state line and Acheson by following Buffalo Creek in Independence and Donegal Townships.

[5] On August 30, 2005, the Pennsylvania Department of Transportation (PennDOT) closed and later removed one of the bridges over Buffalo Creek due to safety concerns.