The route is mostly a two-lane road that passes through rural areas in the northern part of McKean County.

PA 346 begins at the Pennsylvania–New York state line in the Allegheny National Forest as a continuation of NY 280.

It then passes former St. Bernard Elementary and a cemetery before entering the city of Bradford just west of the Interstate Parkway.

After numerous changes in direction, PA 346 reaches Hazelton Mills and leaves the dense forest for a suburb of Bradford.

In Hazelton Mills, the route turns northeast and enters the city of Bradford as West Washington Street.

Two blocks north, the route turns east again, this time on Forman Street, and crosses the Buffalo and Pittsburgh Railroad's Bradford Industrial Track line.

US 219 and PA 346 run northeast through Bradford, passing through the industrial sector of the city, where it heads over the Buffalo and Pittsburgh Railroad tracks.

After crossing East Main Street, the route leaves the city of Bradford and changes names to Derrick Road as it enters Foster Township.

As a result, PA 346 was rerouted slightly on its existing western end to head northwest to the state line, where it connected to the rebuilt NY 280.