PA 481 begins at an intersection with US 40 in the borough of Centerville, heading northwest on two-lane undivided Old National Pike.

The road makes a turn east into woods before curving north into a mix of farmland and forests with occasional homes.

Farther north, the route comes into Fallowfield Township and passes through Lover, heading northwest before making a turn to the northeast and interchanging with I-70.

The road passes under the PA 43 toll freeway and heads into more forested surroundings, crossing Norfolk Southern's Ellsworth Secondary railroad line and making a turn to the east.

The route turns north into residential areas before curving northeast and heading into the city of Monongahela on Park Avenue.