U.S. Route 15 (US 15) is United States Numbered Highway that runs from Walterboro, South Carolina, north to Painted Post, New York.

One is from East Pennsboro Township, Cumberland County, just north of the I-81 interchange, to just south of Duncannon.

With the adoption of the U.S. Numbered Highway System, US 15 originally terminated at Harrisburg, while US 111 serviced the modern route north of that point.

However, instead of replacing US 111's old routing directly, US 15 ran along the east bank of the Susquehanna River between Harrisburg and Williamsport.

[5] As part of the construction of the Central Susquehanna Valley Thruway, US 15 is planned to be rerouted to the new freeway between Selinsgrove and Union Township, bypassing Shamokin Dam.