PA 452 begins at an intersection with US 13 in the borough of Marcus Hook in Delaware County, heading north-northwest on two-lane undivided Market Street.

South of this intersection, Market Street continues as an unnumbered road toward the Delaware River.

Upon crossing Laughead Avenue, PA 452 heads into Upper Chichester Township and runs north past more homes to the west, widening into a four-lane divided highway as it crosses Marcus Hook Creek and comes to an interchange with I-95.

Past this interchange, the route heads into commercial areas, narrowing back into a two-lane undivided road and coming to a bridge over CSX's Philadelphia Subdivision railroad line.

PA 452 continues to wind north through woodland with some residential and commercial development, running a short distance to the west of Chester Creek.