Pennsylvania Route 53 is an 83-mile-long (134 km) state highway located in central Pennsylvania. The southern terminus of the route is at U.S. Route 219 (US 219) near the borough of Summerhill. The northern terminus is at PA 144 in the Snow Shoe Township community of Moshannon.

U.S. Route 219 (US 219) is a part of the U.S. Highway System that runs from Rich Creek, Virginia, to West Seneca, New York. From near Grantsville, Maryland north to Ebensburg, Pennsylvania, US 219 is Corridor N of the Appalachian Development Highway System. From Meyersdale, Pennsylvania to just south of Carrolltown, Pennsylvania, US 219 is a limited-access highway. From Carrolltown US 219 runs largely as a two-lane road to DuBois, Pennsylvania, through which it runs as Brady Street, and then returns to a two-lane road after a junction with Interstate 80. US 219 runs directly through the towns of Brockway, Ridgway, and Johnsonburg before reaching Wilcox, where PA Route 321 splits and heads for the town of Kane. US 219 continues north as a two-lane road until reaching Bradford, where it becomes a limited-access highway and remains so until reaching the New York border. On August 9, 2007, Pennsylvania State Transportation Secretary Allen D. Biehler unveiled four signs along US Route 219 that dedicated the portion of the route in Somerset County, Pennsylvania as the Flight 93 Memorial Highway.