PA 339 runs north through the Coal Region to Brandonville, where it heads northwest to follow the Catawissa Creek to Mainville.

The road soon passes under a Reading Blue Mountain and Northern Railroad line and runs past homes and businesses.

The road makes a sharp turn west to descend the ridge, entering East Union Township and coming to an intersection with PA 924.

At this point, the two routes head north for a concurrency on Main Boulevard and pass through residential areas in Brandonville.

The road heads northwest through woodland with some fields parallel to the creek, entering North Union Township.

The road winds northwest through rural areas parallel to the creek, crossing it for a third time and turning north.

[2][3] PA 339 heads into Beaver Township in Columbia County and becomes State Road, curving northwest and passing through a mix of fields and woods with some homes.

The road turns northwest and runs parallel to the Catawissa Creek through rural areas, heading into Main Township and becoming Mainville Drive.

The route leaves Mifflinville and becomes Mifflin Nescopeck Highway, running between farmland to the south and Norfolk Southern's Sunbury Line and the Susquehanna River parallel to the north.

PA 339 bends northeast and crosses the railroad tracks, continuing through farmland and woodland with the Norfolk Southern line parallel to the south and the river further north.

The route turns north onto Broad Street and passes through residential areas before it reaches its northern terminus at an intersection with PA 93.