The route passes through suburban areas in Delaware and Montgomery counties to the west of Philadelphia, serving Swarthmore, Springfield, Broomall, Villanova, and Gulph Mills.

The streets head northwest through urban development, crossing under Amtrak's Northeast Corridor railroad line.

The road passes homes and businesses, running to the west of Widener University, with a brief stretch of divided highway at the 15th Street intersection.

The route narrows to two lanes and crosses the Ridley Creek, at which point it leaves Chester and enters Nether Providence Township.

PA 320 becomes a three-lane road with a center left-turn lane and comes to a bridge over Crum Creek, where it enters a small exclave of Springfield Township, and I-476.

The route narrows back into a two-lane undivided road and comes to a bridge over SEPTA's light rail Media–Sharon Hill Line east of the Springfield Mall station.

[2][3] Past the US 1 interchange, PA 320 passes more commercial establishments and crosses into Marple Township, becoming a four-lane undivided road.

The route passes over I-476 again and intersects Springfield Road immediately after that, at which point it becomes a five-lane road with a center left-turn lane and passes between a large cemetery to the west and Cardinal O'Hara High School and some woods to the east.

The road becomes a four-lane divided highway as it runs past businesses along with some nearby residential areas.

The road runs through wooded residential areas, crossing the Darby Creek into Haverford Township.

The route heads northeast and passes under SEPTA's Norristown High Speed Line before coming to an intersection with US 30 (Lancaster Avenue) in the community of Villanova.

Following this, PA 320 becomes North Spring Mill Road and runs between residential neighborhoods to the northwest and Villanova University to the southeast.

The road passes over Amtrak's Keystone Corridor railroad line west of the Villanova station serving SEPTA's Paoli/Thorndale Line, with a right-in/right-out access point serving the university and the station, before running through more of the university campus.

One block after County Line Road, PA 320 turns northwest onto Montgomery Avenue, curving north and crossing under I-476 again.

in Chester north to PA 23 at the intersection of Spring Mill Road and Montgomery Avenue in Lower Merion Township.

[11] In the later part of the 20th century, PA 320 saw increasing traffic levels as it served as one of the main north–south routes through Delaware County.

[12] In January 2020, a construction project began to reconstruct and realign PA 320 away from Hanging Rock in Upper Merion Township.