The road passes south of warehouses and comes to a diamond interchange with PA 863. Following this interchange, the freeway heads to the south of more warehouses and runs through more rural areas with some homes, crossing into Upper Macungie Township. I-78/US 22 runs between farm fields to the north and warehouses and industrial development to the south before it comes to a cloverleaf interchange with PA 100 in a business area in the community of Fogelsville. After the PA 100 interchange, the freeway widens to six lanes and heads east through industrial areas, coming to a bridge over Norfolk Southern's C&F Secondary railroad line before curving northeast. In the community of Kuhnsville, US 22 splits from I-78 at an eastbound exit and westbound entrance by heading northeast on the Lehigh Valley Thruway. From here, I-78 continues east-southeast as a four-lane freeway, passing residential subdivisions with some commercial development. The freeway continues southeast and passes over I-476 (Pennsylvania Turnpike Northeast Extension) before it comes to a westbound exit and eastbound entrance with the PA 309 freeway. At this point, PA 309 becomes concurrent with I-78 and the freeway enters Lower Macungie Township, widening to six lanes and running past commercial development to the southwest of Dorney Park & Wildwater Kingdom. The freeway reaches a partial cloverleaf interchange with the northern terminus of US 222 and the southern terminus of PA 222 at Hamilton Boulevard, which provides access to the cities of Allentown and Reading. Following this interchange, the road crosses into South Whitehall Township and heads east between residential areas to the north and farm fields to the south before entering Salisbury Township and heading north of Lehigh Valley Hospital-Cedar Crest. Past the hospital, I-78/PA 309 comes to an interchange with the northern terminus of the southern section of PA 29 at Cedar Crest Boulevard before running between residential areas to the north and office buildings to the south. The freeway enters the city of Allentown and runs through woodland, crossing Little Lehigh Creek before it passes through a small section of Salisbury Township. The road heads back into Allentown and runs near residential areas, passing south of Allentown Queen City Municipal Airport before it comes to the Lehigh Street exit. I-78/PA 309 runs near industrial areas and passes over Norfolk Southern's Reading Line before coming to a westbound exit ramp serving Emaus Avenue. The freeway passes near neighborhoods before it leaves Allentown for Salisbury Township, where it ascends forested South Mountain.