U.S. Route 222 is a U.S. Highway that is a spur of US 22 in the states of Maryland and Pennsylvania. It runs for 95 miles (153 km) from US 1 in Conowingo, Maryland, north to the junction of Interstate 78 (I-78) and Pennsylvania Route 309 in Dorneyville, Pennsylvania. US 222 is almost entirely in Pennsylvania, and serves as the state's principal artery between the Lancaster and Reading areas in the west and the Lehigh Valley in the east.

U.S. Route 1 (US 1) is the easternmost and longest of the major north–south routes of the older 1920s era United States Numbered Highway System, running from Key West, Florida, to Fort Kent, Maine. In the U.S. state of Maryland, it runs 81 miles (130 km) from the Washington, D.C. line to the Pennsylvania state line near the town of Rising Sun.