The route runs southwest to northeast and serves as a major arterial road through the city of Philadelphia and for many of the suburbs in the Delaware Valley metropolitan area.

US 1 enters Pennsylvania from Maryland in West Nottingham Township, Chester County, heading northeast as a two-lane undivided road that soon widens into a four-lane divided highway.

The road curves north and runs through fields and woods with some development, becoming a four-lane freeway that is called the Kennett–Oxford Bypass and dedicated as the John H. Ware III Memorial Highway.

US 1 continues through farmfields and woods and crosses the West Branch Big Elk Creek before it heads into Upper Oxford Township, where it has a partial cloverleaf interchange with PA 896.

[2][3] The freeway crosses Big Elk Creek into Penn Township and heads east to a diamond interchange at PA 796 north of the community of Jennersville.

The route heads through wooded areas with some nearby residential development and crosses West Branch Red Clay Creek before it skirts into the southern portion of East Marlborough Township, where it has a diamond interchange with PA 82 north of the borough of Kennett Square.

The road heads into wooded areas with some homes and businesses, at which point PA 52 splits in the community of Hamorton to continue southeast toward the city of Wilmington, Delaware.

Here, US 322 heads north along US 202 and turns east to join US 1 in a concurrency along Baltimore Pike, running past more commercial establishments in Concord Township.

In Concordville, US 322 splits to the southeast and US 1 continues along Baltimore Pike, intersecting Concord Road before heading into more wooded areas with occasional businesses and crossing the West Branch Chester Creek.

[2][4] The route curves to the east and enters the borough of Chester Heights, running past businesses before heading into forested areas, where it passes north of the corporate headquarters of Wawa.

Following this, the route continues east and passes between the Promenade at Granite Run residential and retail center to the north and Riddle Hospital to the south, coming to an interchange with PA 352.

The route crosses into Springfield Township and reaches a diamond interchange with PA 320, with the southbound exit providing access to the shopping center.

US 1 passes to the southeast of Lankenau Medical Center before it crosses East Branch Indian Creek and reaches an intersection with US 30 (Lancaster Avenue).

US 1 becomes lined with businesses as it passes between the Lower Merion Township community of Bala Cynwyd to the northwest and the Philadelphia neighborhood of Wynnefield to the southeast.

The route comes to a bridge over SEPTA's Cynwyd Line south of Bala station before it reaches an intersection with the eastern terminus of PA 23 and Conshohocken Avenue.

From here, the freeway heads into the East Falls neighborhood and passes near urban residential and commercial development, coming to a southbound exit and northbound entrance serving Ridge Avenue and Kelly Drive.

[2][5] After passing through the park, US 1 heads through residential areas, before running past businesses and coming to an intersection with the southern terminus of PA 532 at Welsh Road.

From here, US 1 becomes the Martin Luther King Jr. Memorial Highway and passes near several businesses before coming to a partial cloverleaf interchange with Rockhill Drive, which provides access to the Neshaminy Mall to the east of the road.

The route passes between an office park to the west and the shopping mall to the east before it heads into wooded areas and crosses Neshaminy Creek.

Upon crossing the creek, the freeway heads into Middletown Township and comes to a northbound exit and southbound entrance with the southern terminus of US 1 Business (US 1 Bus.).

The route curves to the east-northeast and runs through residential areas, crossing into the borough of Langhorne Manor, where it has a northbound exit and southbound entrance at Hulmeville Avenue.

The freeway heads back into Middletown Township again and comes to an interchange providing a connection to PA 413 via South Bellevue and East Gillam avenues.

From here, the freeway fully enters Falls Township and runs between woodland to the north and industrial areas to the south, continuing to an interchange with Stony Hill Road and the northern terminus of US 1 Bus.

A short distance later, US 1 comes to a partial cloverleaf interchange with the northern terminus of the US 13 freeway and Pine Grove Road, where the ramp from southbound US 1 to US 1 Bus.

At this point, the freeway curves to the northeast and runs through wooded areas with nearby residential and commercial development, entering the borough of Morrisville.

Between Philadelphia and Trenton, US 1 is a part of the Lincoln Highway, a cross-country auto trail that ran from San Francisco east to New York City.

[9] From near Hornig Road in Northeast Philadelphia, the old alignment heads through woods, closed to traffic, paralleling powerlines, after which it was upgraded on the spot to become Roosevelt Boulevard.

On November 21, 1988, an act of the Pennsylvania General Assembly designated the portion of US 1 in Bucks County between the Pennsylvania Turnpike and the New Jersey border as the Martin Luther King Jr. Expressway after civil rights leader Martin Luther King Jr.[11] On June 14, 2000, the Roosevelt Boulevard portion of US 1 was designated the police officer Daniel Faulkner Memorial Highway in memory of Daniel Faulkner, an officer of the Philadelphia Police Department who was murdered by Mumia Abu-Jamal in 1981.

[12][13] On May 31, 2002, the US 1 freeway in Chester County between the Maryland border and Kennett Square was designated the John H. Ware III Memorial Highway in honor of John H. Ware III, a politician from Oxford that served in the Pennsylvania State Senate and U.S. House of Representatives and pushed for the construction of the US 1 freeway in Chester County.

[15] On October 29, 2018, work began on a project to reconstruct and widen the portion of US 1 between Old Lincoln Highway and the Rockhill Drive interchange in Bensalem Township.