US 322 enters Pennsylvania from Ohio in West Shenango Township. From this point, the road continues east, forming a concurrency with U.S. Route 6 between Conneaut Lake and Meadville, interchanging with Interstate 79 and intersecting U.S. Route 19 in Meadville. In Franklin, the route crosses U.S. Route 62. Continuing east, US 322 interchanges with Interstate 80 near Clarion before meeting U.S. Route 119 and U.S. Route 219 south of DuBois. US 322 heads southeast as a surface road before merging onto the Interstate 99/U.S. Route 220 freeway in Port Matilda, following that east to State College. The US 322 freeway continues past I-99 before ending to the east of State College. Near Potters Mills, US 322 becomes a freeway again and intersects U.S. Route 22 and U.S. Route 522, forming a long concurrency with the former. The US 22/322 freeway continues across the Appalachian Mountains, meeting U.S. Route 11/U.S. Route 15 prior to crossing the Susquehanna River by way of the Clarks Ferry Bridge. The road continues south along the east bank of the river to Harrisburg, where US 322 splits from US 22 by heading east onto Interstate 81 and then south onto Interstate 83. At the interchange between I-83 and the northern terminus of Interstate 283, US 322 turns east and heads to Hershey, intersecting U.S. Route 422. From this point, US 322 heads southeast through the Pennsylvania Dutch Country, intersecting U.S. Route 222 near Ephrata. In Downingtown, the route crosses U.S. Route 30 before heading to West Chester. Here, US 322 bypasses the town and merges onto a freeway alignment along with U.S. Route 202 that ends to the south of West Chester. US 322 follows US 202 until Painters Crossing, where it turns east onto U.S. Route 1. In Concordville, US 322 splits from US 1 and heads southeast to Chester. In Chester, the route forms a brief concurrency with Interstate 95 before heading southeast and interchanging with U.S. Route 13 prior to the Commodore Barry Bridge over the Delaware River.
New Jersey
US 322 enters New Jersey via the Commodore Barry Bridge just north of Delaware and interchanges with Interstate 295 and the New Jersey Turnpike before entering historic Mullica Hill, New Jersey. In Glassboro, it bisects Rowan University. At Williamstown, US 322 goes onto the "Black Horse Pike" and follows it the rest of the way to Atlantic City, being concurrent with U.S. Route 40 from Mays Landing on east. In the 1960s and 1970s, the New Jersey Department of Transportation had planned for a freeway bypass of U.S. Route 322 around Glassboro. Later it was planned as a New Jersey Turnpike extension, but all plans were dropped due to budget cuts and mounting opposition.