U.S. Route 322 (US 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.

Route description In Pennsylvania, US 322 is signed as 28th Division Highway, in honor of the 28th Infantry Division.

Ohio to Brookville US 322 enters Pennsylvania from Ohio in Crawford County, heading southeast on two-lane undivided Williamsfield Road. The road runs through rural areas on the southwest border of Pymatuning State Park, which is home to the Pymatuning Reservoir. Past the state park, the route crosses into Mercer County and heads into the borough of Jamestown, becoming Gibson Street and coming to an intersection with PA 58. At this point, the two routes head east for a concurrency along Liberty Street, crossing the Shenango River. US 322 splits from PA 58 by turning north onto Depot Street. The route leaves Jamestown and crosses back into Crawford County, becoming an unnamed road. The road curves northeast and comes to the community of Hartstown, where it becomes Liberty Street and reaches an intersection with PA 18. At this point, PA 18 turns northeast for a concurrency with US 322 and the road comes to a bridge over the Canadian National's Bessemer Subdivision railroad line as it curves northeast and continues as an unnamed road. Farther northeast, the road enters the borough of Conneaut Lake and becomes State Street, turning north onto South 4th Street to come to an intersection with US 6/PA 285 in the center of the borough. At this point, US 322/PA 18 turn east to join US 6 and PA 285 on Water Street. A block later, PA 285 splits to the south. US 6/US 322/PA 18 become a five-lane road with a center left-turn lane and head east out of the borough, passing to the south of Conneaut Lake. PA 18 splits from US 6/US 322 by turning to the north, with US 6/US 322 continuing east-northeast on Conneaut Lake Road. The road heads into a business area to the west of the city of Meadville and comes to a roundabout with US 19 and the southern terminus of PA 98, at which point US 19 becomes concurrent with US 6 and US 322. The roadway becomes a four-lane divided highway and comes to a cloverleaf interchange with I-79. Past this interchange, the three routes reach an intersection with the southern terminus of PA 102 before curving north and entering Meadville upon crossing French Creek and a Western New York and Pennsylvania Railroad line. The road becomes French Creek Parkway before US 322 splits from US 6 and US 19 by turning to the east onto two-lane undivided Linden Street. The route runs through developed areas and turns south onto South Main Street before leaving Meadville. The road becomes Cochranton Road and runs through rural areas to the east of French Creek and the Western New York and Pennsylvania Railroad line. US 322 curves to the southeast and the name changes to Meadville Road. The route becomes an unnamed road and passes through the northern part of the borough of Cochranton before it comes to an intersection with PA 173. Past this intersection, the road curves to the south. The route crosses into Mercer County, where it makes a turn to the east.

US 322 heads into Venango County and runs east, curving southeast in the community of Hannasville. The road enters the borough of Sugarcreek, where it crosses Sugar Creek and comes to an intersection with the southern terminus of PA 427. From here, the route curves south to run east of the parallel Sugar Creek before turning east and running north of French Creek and the Western New York and Pennsylvania Railroad line. US 322 turns south alongside the creek and railroad tracks before it curves east and enters the city of Franklin. At this point, the road becomes Grant Street and passes through developed areas of the city, curving northeast and back to the east. US 322 reaches an intersection with the southern terminus of PA 417, at which point it turns south onto four-lane undivided 13th Street, crossing the Western New York and Pennsylvania Railroad line at-grade. The road turns into a divided highway and crosses French Creek, becoming undivided again and heading into the downtown area of Franklin. US 322 comes to an intersection with US 62/PA 8, at which point it turns east for a concurrency with the two routes on four-lane undivided Liberty Street. The road turns southeast and leaves the downtown area, narrowing to one lane westbound before US 62/PA 8 split from US 322 by turning to the northeast. US 322 continues south along two-lane undivided Liberty Street before it turns east onto 8th Street and crosses the Allegheny River, leaving Franklin. From here, the route becomes an unnamed road and curves south parallel to the river, running through rural areas. The road turns to the east and passes through the community of Venango before the Allegheny River curves south away from the road, with the road gaining a second eastbound lane as it climbs a hill. US 322 narrows to two lanes prior to reaching the community of Cranberry. Here, the route passes businesses and heads to the south of the Cranberry Mall before it intersects the southern terminus of PA 257. Past this intersection, the road runs through rural land, crossing East Sandy Creek and reaching a junction with the northern terminus of PA 38.

US 322 enters Clarion County and continues southeast, intersecting the eastern terminus of PA 338 in the community of Kossuth. Farther east, the road reaches the borough of Shippenville. Upon entering Shippenville, the route becomes Main Street and intersects PA 208. At this point, PA 208 joins US 322 in a concurrency before it splits to the north. The route leaves Shippenville and becomes unnamed again, passing south of a residential development. The road reaches an intersection with PA 66 near businesses in the community of Marianne. Past this intersection, US 322 runs southeast through rural areas before it gains a second westbound lane as it descends a hill. The route narrows to two lanes and curves east, crossing the Clarion River. After crossing the river, the road gains a second eastbound lane as it ascends a hill. US 322 curves south and enters the borough of Clarion, where it narrows to two lanes and becomes North 1st Avenue, running through developed areas and passing east of Memorial Stadium. The route turns southeast onto Main Street and heads into the downtown area of Clarion, where it intersects the eastern terminus of PA 68. After leaving the downtown area, the road passes through the PennWest Clarion university campus. US 322 leaves Clarion and becomes an unnamed road, passing east through rural areas. Farther east, the route enters the borough of Strattanville and runs east through the borough along Main Street. The road leaves Strattanville and becomes unnamed, heading east-southeast and reaching a partial cloverleaf interchange with I-80.

US 322 crosses into Jefferson County and enters the borough of Corsica, where it becomes Main Street, forming a concurrency with PA 949 before that route splits to the south. Upon leaving Corsica, the route turns into an unnamed road and runs a short distance to the south of I-80, passing through the community of Roseville and curving to the east-southeast.

Brookville to State College Farther east, the road enters the borough of Brookville and becomes West Main Street, continuing into an area of businesses and coming to an intersection where PA 28 heads south and PA 36 and PA 28 Truck heads north. At this point, US 322 forms a concurrency with PA 28 and PA 36, running through developed areas of the borough. The road becomes Main Street and PA 36 splits from US 322/PA 28 by heading to the south, with US 322/PA 28 continuing east through the downtown area of Brookville. The road curves northeast and southeast out of the downtown area before crossing the North Fork Creek and running east along East Main Street. On the eastern border of Brookville, PA 28 splits to the east and US 322 continues southeast through rural areas as an unnamed road, crossing Mill Creek in the community of Port Barnett. The route passes through the community of Emerickville as it continues along. Farther east, the road turns to the south and enters the borough of Reynoldsville, where the name becomes West Main Street and it curves east. US 322 continues southeast and comes to an intersection with the southern terminus of PA 950 before it crosses a Buffalo and Pittsburgh Railroad line at-grade and Sandy Lick Creek. The route becomes East Main Street and runs through the downtown area of Reynoldsville, where it has a junction with the northern terminus of PA 310. US 322 leaves Reynoldsville becomes an unnamed road and continues through rural areas, curving northeast in the community of Prescottville. The route continues east and runs through the community of Rathmel.

US 322 enters Clearfield County and runs east-southeast along Behringer Highway, coming to an intersection with US 119 south of the city of DuBois. The route continues east and reaches a junction with US 219, where it briefly becomes a divided highway. At this point, US 219 joins US 322 in a concurrency along two-lane undivided Carson Hill Road. The two routes pass over a Buffalo and Pittsburgh Railroad line and head southeast, passing through the community of Salem. The road reaches the community of Luthersburg, where it intersects the eastern terminus of PA 410. The two routes curve east onto Luthersburg-Rockton Road and US 219 splits from US 322 by turning to the south. US 322 continues east, curving northeast before reaching the community of Rockton. In Rockton, the route turns east and becomes Rockton Mountain Highway, entering the Moshannon State Forest. Upon entering the state forest, the road turns southeast, crossing Anderson Creek, and then turning northeast before curving to the east. Farther east, US 322 reaches an intersection with PA 153, where it turns southeast to form a concurrency with that route on four-lane divided Rockton Mountain Highway. The road leaves the Moshannon State Forest and continues through rural areas. The two routes enter more developed areas north of the borough of Clearfield as a three-lane road with a center left-turn lane, crossing a R.J. Corman Railroad line at-grade. US 322/PA 153 curve south onto West Front Street and enter the borough of Clearfield. The two routes turn southeast onto two-lane Nichols Street and cross the West Branch Susquehanna River, with the road name becoming Bridge Street. PA 153 splits from US 322 on the east bank of the river by turning south, with US 322 continuing east along Bridge Street before curving north onto Bigler Avenue. The route turns east-southeast as it continues through the borough.