The route passes through industrial areas near the river in Delaware County, serving Chester, Eddystone, Essington, and Lester.

The route crosses the Schuylkill River on the George C. Platt Memorial Bridge and continues along Penrose Avenue to I-76.

The two routes make a sharp curve to the northeast and become West 2nd Street, crossing into the city of Chester and running through urban residential and industrial areas.

US 13/PA 291 continues northeast and becomes a five-lane road with a center left-turn lane as it passes more urban development and empty lots.

At this point, PA 291 runs between Amtrak's Northeast Corridor railroad line to the northwest and State Correctional Institution – Chester to the southeast before intersecting Harrah's Boulevard, which provides access to Harrah's Philadelphia casino and harness racetrack to the southeast along the Delaware River.

The route crosses the Crum Creek into Ridley Township and passes through Boeing Defense, Space & Security's Vertical Lift helicopter plant.

Past this, the Chester Industrial Track heads farther south from the road as it passes more commercial establishments.

The route crosses the Darby Creek into Tinicum Township and runs east past businesses and private airport parking lots, intersecting the southern terminus of PA 420 to the north of the community of Essington.

[4][5] Past this intersection, PA 291 continues east through commercial areas with some homes, becoming Governor Printz Boulevard.

The route heads northeast into the community of Lester, where it passes north of a private airport parking lot and splits into the one-way pair of South Governor Printz Boulevard eastbound and North Governor Printz Boulevard westbound, carrying two lanes in each direction and passing more development.

The two directions rejoin as a four-lane divided highway with a wide median that runs near commercial establishments, heading to the south of an office park and coming to a ramp from northbound I-95 to eastbound PA 291 that merges in from the left.

From here, the route continues east as four-lane divided Industrial Highway between I-95 to the north and a lake to the south, coming to a bridge over CSAO's Chester Secondary railroad line.

The route continues northeast parallel to the Airport Line, reaching a partial interchange with I-95 that has ramps to and from the southbound lanes of I-95.

[4][6] After crossing the river, the bridge passes over part of the large former Philadelphia Energy Solutions oil refinery.

Past this intersection, the road passes under a CSAO railroad spur and CSX's Harrisburg Subdivision railroad line before intersecting Pattison Avenue, which heads east to the South Philadelphia Sports Complex, and becoming a five-lane road with a center left-turn lane, running past homes and businesses in South Philadelphia.

[14] Plans for the PA 291 freeway were dropped in the 1970s because the Pennsylvania Department of Transportation halted a number of road projects due to funding issues.