PA 655 begins at the Maryland border in Thompson Township in Fulton County, where the road continues south into that state as North Pennsylvania Avenue toward the town of Hancock.

From the state line, the route heads north on two-lane undivided Thompson Road, passing through a mix of farmland and woodland with some homes.

PA 655 crosses into Belfast Township and runs through agricultural areas and woods before it bends west and heads into the residential community of Needmore, where it comes to an intersection with US 522.

At this point, PA 655 turns north for a concurrency with US 522 on Great Cove Road, passing through a mix of farmland and development and curving northeast and east.

The route turns north to remain along Pleasant Ridge Road and heads north-northeast through forested areas with some farm fields and homes, passing through the community of Andover.

The road winds through more rural areas a short distance to the west of Licking Creek, reaching an intersection with US 30 in the community of Harrisonville.

[4][5] PA 655 enters Clay Township in Huntingdon County and heads north through farmland with some homes before turning northeast and northwest.

The route leaves Saltillo for Clay Township again and becomes an unnamed road, passing through a mix of farm fields and woodland with some residences.

Farther north, PA 655 passes through the community of Barneytown and heads into Union Township, where it continues into more forested areas with some fields and residences.

The road leaves Mill Creek for Brady Township and heads north-northeast through forests before turning northeast through the community of Fousetown.

[4][6] PA 655 enters Menno Township in Mifflin County and continues northeast through agricultural areas in the Kishacoquillas Valley as an unnamed road.

Farther northeast, the route passes businesses and becomes a divided highway, curving east to reach a diamond interchange with the US 322 freeway.

PA 655 widens to four lanes and comes to its northern terminus at an intersection with SR 1005 (Tea Creek Road/North Main Street) north of the community of Reedsville.