At its western edge, the route leaves the freeway and travels as a four-laner along the Shenango River.

Closer to its eastern edge, it passes commercial development, and 422 Business joins with US 422 as its freeway segment ends.

After serving as the major Water Street, the route winds out of Kittanning toward the edge of the bypass.

Despite functioning as a business route for a freeway bypass, the road does not completely follow its parent's original path, nor does it enter the city center.

It instead encompasses a much more rural path, starting in the west on Pike Avenue near the outskirts of Indiana, then corresponding with Warren Road and Indian Springs Road, before reaching some development on Wayne Avenue, as it meets back up with the freeway.

heads east from US 222/US 422 along Penn Avenue, passing through Wyomissing and West Reading.

The business route heads into the eastern part of the city southeast on Perkiomen Avenue before following the one-way pair of Perkiomen Avenue eastbound and Mineral Spring Road westbound into Mount Penn.

continues along Perkiomen Avenue to St. Lawrence, where it intersects the western terminus of PA 562 and turns southeast.

[4][5] In 1928, the US 120/PA 13 designation between Reading and Philadelphia was changed to US 422/PA 17 in order to provide for one number for the Benjamin Franklin Highway.

[14] The alternate route was decommissioned in 1964 following the rerouting of US 422 to the West Shore Bypass and the establishment of US 422 Bus.

left Norristown and became Ridge Pike, continuing southeast through suburban areas to Barren Hill.

The route entered Philadelphia and became Germantown Avenue, passing through the Chestnut Hill section of the city.

The alternate route headed southeast onto Clarissa Street and reached its eastern terminus at US 1/US 13 (Hunting Park Avenue).

was first designated by 1950, following Main Street through Norristown before continuing along Ridge Pike through Barren Hill.

The alternate route continued into Philadelphia and ran southeast on Ridge Avenue, ending at an intersection with US 1 Byp./US 13 Byp.

crossed into Philadelphia and became Germantown Avenue, passing through the Chestnut Hill neighborhood.

continued east onto Tabor Street and reached its eastern terminus at an intersection with US 1 Byp./US 13 Byp./US 422 (Roosevelt Boulevard).