Pennsylvania Route 16 is a 43-mile-long (69 km) east–west state route located in southern Pennsylvania, United States. The western terminus of the route is at U.S. Route 522 in McConnellsburg. The eastern terminus is at the Mason–Dixon line in Liberty Township, where the road continues into Maryland as Maryland Route 140. PA 16 is a two-lane road that runs through rural areas in Fulton, Franklin, and Adams counties. The route heads east from McConnellsburg and crosses Tuscarora Mountain into Franklin County, where it continues east into the agricultural Cumberland Valley. Here, the passes through Mercersburg, Greencastle, and Waynesboro. PA 16 heads east through the South Mountain range, where it heads into Adams County and passes through Carroll Valley before coming to the Maryland border. PA 16 intersects several roads including PA 456 in Cove Gap, PA 75 and PA 416 in Mercersburg, PA 995 in Upton, US 11 and Interstate 81 (I-81) in Greencastle, PA 316 and PA 997 in Waynesboro, and PA 116 in Carroll Valley. The road's main name is Buchanan Trail in honor of 15th President James Buchanan, who was born near the road in Cove Gap.

U.S. Route 522 is a spur route of US 22 in the states of Virginia, West Virginia, Maryland, and Pennsylvania. The U.S. Highway travels in a north-south direction, and runs 308.59 miles (496.63 km) from US 60 near Powhatan, Virginia, to its northern terminus at US 11 and US 15 near Selinsgrove, Pennsylvania. US 522 serves many small cities and towns in the Piedmont, Blue Ridge Mountains, and northern Shenandoah Valley of Virginia. The highway serves the Virginia communities of Goochland, Mineral, Culpeper, the town of Washington, and Front Royal and the independent city of Winchester. US 522 then follows the Ridge-and-Valley Appalachians north and then east through the Eastern Panhandle of West Virginia, a 2-mile-wide (3.2 km) stretch of Western Maryland, and South Central Pennsylvania to its terminus in the Susquehanna Valley. The highway serves Berkeley Springs, West Virginia; Hancock, Maryland; and the Pennsylvania communities of McConnellsburg, Mount Union, Lewistown, and Middleburg.