The route interchanges with the PA 12 freeway and continues north through suburban Muhlenberg Township as 5th Street Highway.

was extended north to its current terminus following the rerouting of US 222 to a new outer bypass of Reading.

The road passes through the community of Montrose before it comes to an intersection with PA 724, where it widens to a four-lane divided highway.

The road briefly runs along the border between the borough of Wyomissing to the north and Cumru Township to the south before it crosses Wyomissing Creek and enters the borough of Shillington, where it narrows to a two-lane undivided road past homes and some businesses that runs east-southeast.

splits from PA 724 by continuing northeast on Lancaster Avenue, a three-lane road with a center left-turn lane that passes through residential areas with some commercial establishments, heading to the north of Governor Mifflin Senior High School.

The route forms the border between Shillington to the northwest and Cumru Township to the southeast, passing between shopping centers to the south and neighborhoods to the north, before it fully enters Cumru Township and runs through the community of Clover Park.

becomes a four-lane undivided road and continues through residential and business areas as it forms the border between the city of Reading to the northwest and the borough of Kenhorst to the southeast, fully entering Reading at the Kenhorst Boulevard intersection.

Past this intersection, the route passes under Norfolk Southern's Harrisburg Line #1 and continues through urban areas of homes and businesses.

curves north and intersects the northern terminus of PA 10 and passes under the Schuylkill River Trail before it reaches an interchange with the US 422 freeway (West Shore Bypass).

The road passes more urban homes before heading into the commercial downtown of Reading, where it intersects the eastbound direction of US 422 Bus.

The route intersects the beginning of one-way northbound Centre Avenue, which leads to PA 61, and comes to a bridge over Norfolk Southern's Harrisburg Line #2 before it has a junction with the southern terminus of PA 61 at Greenwich Street.

The route passes between a large cemetery to the west and neighborhoods to the east before it widens to four lanes and heads into commercial areas.

passes under Norfolk Southern's Pottsville Branch and widens into a divided highway, leaving Reading for Muhlenberg Township as it comes to an interchange with the PA 12 freeway (Warren Street Bypass).

[2][3] After the PA 12 interchange, the business route continues north as a four-lane divided highway called North 5th Street Highway through a mix of residential and commercial areas in the community of Hyde Villa.

The route runs past more businesses and narrows to a three-lane road with a center left-turn lane as it passes to the west of the community of South Temple.

reaches its northern terminus at a trumpet interchange with the end of the US 222 freeway bypass of Reading, at which point Allentown Pike continues north as US 222.

[4] In 1916, the road between Reading and Allentown, became a part of the William Penn Highway, an auto trail that ran from Pittsburgh to New York City.

In 1924, the William Penn Highway was designated as PA 3 with the establishment of the first state route numbers in Pennsylvania.

[5] With the establishment of the U.S. Highway System in 1926, the route heading from Reading southwest to Lancaster was designated as US 222 while the route heading from Reading to Allentown along the William Penn Highway was designated as part of US 22, which ran concurrent with PA 3.

In addition, PA 73 ran concurrent with US 222/PA 240 between New Holland Avenue, where it split south, and downtown Reading.

[10][11] In 1931, plans were made to reroute US 22 and the William Penn Highway to a more direct alignment between Harrisburg and Allentown by way of PA 43.