Pennsylvania state highways 16, 75, and 416 all pass through Mercersburg. PA 16 leads east to Greencastle and to Interstate 81, and northwest through Cove Gap and over Tuscarora Mountain 10 miles to McConnellsburg. PA 75 leads north to Fort Loudon and south to the Maryland border. PA 416 leads northeast to U.S. Route 30 near St. Thomas and southeast to the Maryland border. Hagerstown, Maryland, is to the southeast via PA 416 and Maryland Route 58, while Chambersburg, the Franklin County seat, is to the northeast via PA 416 and US 30.