At both ends, PA 462 terminates at U.S. Route 30 (US 30), which follows a mostly freeway alignment parallel to the north between York and Lancaster.

PA 462 continues east through Hallam to Wrightsville and passes through that town before it crosses the Susquehanna River and runs through Columbia.

From this interchange, PA 462 heads northeast on four-lane divided West Market Street through commercial areas, soon narrowing to a three-lane road with a center left-turn lane.

The road passes between industrial areas to the northwest and residential neighborhoods to the southeast before it crosses a York Railway line at-grade.

[2][3] At this point, PA 462 becomes concurrent with PA 74 and the road splits into a city-maintained one-way pair, with the eastbound direction following West Market Street, which is two-way and two lanes wide, and the westbound direction following West Philadelphia Street, which carries two lanes of one-way traffic westbound.

The route crosses a York Railway line at-grade in a commercial area before it runs northeast past more homes and a few businesses.

The route comes to an interchange with I-83, at which point it becomes a divided highway, and enters Springettsbury Township, continuing past more homes in the community of East York as a four-lane undivided road.

The road runs past a mix of residential and commercial development and crosses into Hellam Township, where the name becomes Lincoln Highway.

PA 462 continues past development and enters the borough of Hallam at the Kreutz Creek Road/Freysville Road intersection.

The route leaves Hallam for Hellam Township again and gains a center left-turn lane, passing east-northeast through farmland with some trees and development.

[2][3] PA 462 enters West Hempfield Township in Lancaster County as it begins crossing the river from the western bank.

Upon reaching the eastern bank of the Susquehanna River, PA 462 heads into the borough of Columbia and passes over Norfolk Southern's Port Road Branch railroad line and PA 441 before descending off the Columbia–Wrightsville Bridge and heading northeast into industrial areas on Chestnut Street.

The road gains a center left-turn lane and runs through more residential areas with a few businesses, crossing the Columbia and Reading Railway at-grade.

The route narrows to two lanes and is lined with homes as it heads east through the borough along Main Street.

PA 462 comes to a bridge over Norfolk Southern's Columbia Secondary railroad line and continues through residential areas before it leaves Mountville and becomes the border between West Hempfield Township to the north and Manor Township to the south, with the name changing back to Columbia Avenue and the center left-turn lane returning.

The route crosses Little Conestoga Creek into Lancaster Township and runs through wooded suburban residential neighborhoods, passing north of the WGAL television studios.

The route heads into the commercial downtown of Lancaster, where it intersects one-way southbound US 222/PA 272 at Prince Street.

The route crosses the Conestoga River into East Lampeter Township and becomes a four-lane divided highway, heading into commercial areas and intersecting the western terminus of PA 340 in the community of Bridgeport.

The road runs east-southeast past more suburban development and widens into a four-lane divided highway as it comes to the Strasburg Pike intersection.

The turnpike also opened up settlement to the Northwest Territory past the Ohio River and provided cheap transportation between the coastal areas and the "bread basket" region around Lancaster.

[8] By 1843, the rise of the railroads and the canals reduced the use of the Philadelphia and Lancaster Turnpike, and the road fell into disrepair and saw decreased usage through the later part of the 19th century.

[9] In 1913, this portion of road became part of the Lincoln Highway, an auto trail that ran from San Francisco east to New York City.