The route passes near farmland before heading near homes and businesses, reaching a partial cloverleaf interchange with PA 772 north of the community of Brownstown. Past here, the freeway runs northeast through agricultural areas. Farther along, US 222 curves to the north and comes to a diamond interchange with US 322 southeast of the borough of Ephrata, at which point it crosses into Ephrata Township. The route passes near businesses at the interchange before it turns northeast and runs through wooded areas with some nearby residential development and farm fields. The freeway heads into East Cocalico Township and runs through more woodland before it passes to the southeast of the community of Reamstown. US 222 passes through farmland and comes to a diamond interchange with Colonel Howard Boulevard, which heads west to provide access to PA 272 and east to provide access to the Pennsylvania Turnpike (I-76). Following this, the route passes over the Pennsylvania Turnpike and crosses into Brecknock Township, running through a mix of farm fields and woods with some nearby residential and commercial development as it passes to the southeast of the borough of Adamstown.