PA 346 begins at the Pennsylvania–New York state line in the Allegheny National Forest as a continuation of NY 280. The route runs southeast through the forest along Willow Bay of the Allegheny Reservoir. Soon the route runs east from Warren County to McKean County. Leaving Willow Bay, PA 346 turns southeast again through the National Forest. It passed Bradford Reservoir Marilla followed by the University of Pittsburgh at Bradford, both on the south side of the roadway. It then passes former St. Bernard Elementary and a cemetery before entering the city of Bradford just west of the Interstate Parkway. PA 321.