U.S. Route 322 is a spur of US 22, running from Cleveland, Ohio, east to Atlantic City, New Jersey. In the U.S. state of Pennsylvania, the route runs from the Ohio state line in West Shenango Township southeast to the Commodore Barry Bridge over the Delaware River in Chester, at which point the route crosses into New Jersey, meeting the New Jersey Turnpike at exit 2. The route passes near or through several cities, including Meadville, DuBois, State College, and Harrisburg. US 322 in Pennsylvania is named the 28th Division Highway in honor of the 28th Infantry Division.

U.S. Route 22 (US 22) is an east–west United States Numbered Highway that stretches from Cincinnati, Ohio, in the west, to Newark, New Jersey, in the east. In Pennsylvania, the route runs for 338.20 miles (544.28 km) between the West Virginia state line in Washington County, where it is a freeway through the western suburbs of Pittsburgh, and then runs east to Easton and the Pennsylvania–New Jersey state line in the Lehigh Valley region of eastern Pennsylvania.