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 splits from PA 272, which becomes signed again, by heading east concurrent with US 30 on an eight-lane freeway, passing near developed areas. US 222 splits from US 30 at a trumpet interchange and heads north onto a four-lane freeway. The route curves northeast and runs through a mix of farmland and residential and commercial development. The freeway comes to a northbound exit and entrance with Butter Road, which provides access to PA 272 via Jake Landis Road, and a southbound exit and entrance with PA 272. Past this interchange, US 222 continues through a mix of farm fields and woodland, passing through a corner of Warwick Township before crossing the Cocalico Creek into West Earl Township.