The northern terminus is at an interchange with U.S. Route 22 (US 22) in North Fayette Township.

From West Pike Street in Canonsburg to US 22, PA 980 runs concurrently with BicyclePA Route A.

From there, the route runs northbound through the borough of Canonsburg, intersecting with Morganza Road which provides access to Exit 45 of I-79.

In 1936, the route was moved from Imperial to Carnot, to its current location.

In 1965, its northern terminus was moved from the William Penn Highway to its current location at the junction with US 22.