The line runs from Philadelphia, where it meets the Northeast Corridor at Zoo Junction at milepost 1.9, west to Harrisburg (MP 104.6), where electrification ends.

The Pennsylvania Railroad originally electrified this line in the 1930s, but it fell into disuse in the 1980s under Amtrak's traction power system.

[7][8][9][10] In the 2000s, there was discussion of initiating commuter rail service from Lancaster to Harrisburg, known as the Capital Red Rose Corridor, but the proposal was subsequently abandoned.

SEPTA Regional Rail Paoli/Thorndale Line trains operate east of Thorndale, with the rights to continue revenue service west to Parkesburg and to run west to Cork Interlocking just east of Amtrak's Lancaster station to reverse direction.

[1] The Commonwealth of Pennsylvania provides the subsidies for Amtrak for the Keystone Service and Pennsylvanian passenger routes that operate on this line.