U.S. Route 11 (US 11) roughly parallels Interstate 81 (I-81) in the U.S. state of Pennsylvania. The route runs from the Maryland state line in Antrim Township, Franklin County, northeast to the New York state line in Great Bend Township, Susquehanna County. US 11 serves Harrisburg, Wilkes-Barre, and Scranton. Between Harrisburg and Scranton, US 11 follows the Susquehanna River, while I-81 follows a shorter route over the mountains further to the east.

Interstate 81 (I-81) is a north–south Interstate Highway, stretching from Dandridge, Tennessee, northeast to Fisher's Landing, New York, at the Canada–United States border. In Pennsylvania, I-81 runs for 232.76 miles (374.59 km) from the Maryland state line northeast to the New York state line near Hallstead and is called the American Legion Memorial Highway. The interstate enters the state near the borough of Greencastle, serving the boroughs of Chambersburg and Carlisle, before reaching Harrisburg, the capital. After that, it climbs into the Pocono Mountains to run through the Wyoming Valley, then exits into New York. It is the longest north–south Interstate in Pennsylvania.