The route passes through suburban areas of Delaware and Chester counties west of Philadelphia, serving Parkside, Brookhaven, Elwyn, Lima, Gradyville, and Goshenville.

South of US 13 Bus., the road continues as unnumbered Avenue of the States through downtown Chester to an intersection with US 13/PA 291 near the Delaware River.

Past here, the route heads north-northwest as a two-lane undivided road, passing more homes and commercial establishments.

Past this, the road heads northwest between the Williamson Free School of Mechanical Trades to the west and the Elwyn Institute to the east.

After this interchange, PA 352 becomes a two-lane divided highway called Middletown Road as it curves to the west, passing between fields and woods with some homes to the northeast and the Promenade at Granite Run residential and retail center to the southwest.

The route becomes a two-lane undivided road and runs through wooded areas of homes and some commercial establishments, coming to an intersection with the northern terminus of PA 452 in the community of Lima.

[2][3] Past this intersection, the road curves north through commercial areas, heading to the east of the Pennsylvania State Police Crime Lab and the Delaware County Juvenile Detention Center.

PA 352 continues north and passes between the Penn State Brandywine university campus to the west and wooded residential areas to the east.

The route curves northwest and crosses into Edgmont Township, where it runs between woods and some homes to the southwest and forests and fields in Ridley Creek State Park to the northeast.

The route continues north past more homes, passing to the east of the community and golf course of Hershey Mill.

The route passes under Amtrak's Keystone Corridor railroad line and heads into commercial areas, coming to a bridge over Norfolk Southern's Dale Secondary.