Both directions of US 222/PA 272 continue north along four-lane undivided North Duke Street and the road reaches the Thaddeus Stevens Bridge over Amtrak's Keystone Corridor, where it becomes the border between Manheim Township to the west and Lancaster to the east. At Keller Avenue, the road becomes Lititz Pike and fully enters Manheim Township, running through commercial areas as a five-lane road with a center left-turn lane. Northbound US 222 and PA 272 head northeast onto Oregon Pike, with PA 272 becoming signed again, while southbound US 222 and PA 501 continue north along Lititz Pike. The two routes continue northeast as a three-lane road with a center left-turn lane and runs past businesses and a few homes before it comes to an interchange with the US 30 freeway. Here, US 222 heads east along US 30 and PA 272 continues northeast along Oregon Pike, passing through commercial areas and narrowing to two lanes. The road continues through suburban areas of homes and businesses and passes through the community of Roseville. Farther northeast, the route widens to a divided highway at the Landis Valley Road intersection, where it passes to the southeast of the Landis Valley Museum in the community of Landis Valley. PA 272 becomes undivided again and passes through wooded residential areas before it enters farmland. The route becomes parallel to the US 222 freeway located to the southeast and reaches direct ramps to and from the southbound lanes of US 222. Access to and from the northbound lanes is provided by Jake Landis Road, which passes under US 222 and connects to Butter Road, which provides access to the ramps. The route heads through wooded areas and passes over Lititz Run before it comes to the eastern terminus of PA 722 near the community of Oregon.