Plans for a limited-access route along the Delaware River in the Philadelphia area originated in the 1930s when both a parkway and elevated highway were proposed; neither of these were built.

I-95 continues east-northeast through woods and heads to the south of CSX Transportation's Twin Oaks Rail Yard, an automotive unloading facility.

At this point, US 322 becomes concurrent with I-95 and the roadway enters the city of Chester, gaining a fourth northbound lane and passing through urban residential neighborhoods.

US 322 provides access from I-95 to the Chester Waterfront and Subaru Park, the home stadium of the Philadelphia Union of Major League Soccer.

[4][5] From here, I-95 heads back into the city of Chester and runs between CSX Transportation's Philadelphia Subdivision railroad line to the northwest and urban areas to the southeast, coming to a northbound exit and southbound entrance with Kerlin Street.

The road curves east-northeast and enters the southern edge of the borough of Ridley Park, running to the north of Boeing Defense, Space & Security's Vertical Lift helicopter plant.

Past this interchange, the highway curves southeast before coming to a bridge over Darby Creek, at which point it enters Tinicum Township.

Past this interchange, the eight-lane freeway continues between marshland in the John Heinz National Wildlife Refuge at Tinicum to the north and developed areas to the south.

Past this, the freeway comes to a bridge over Conrail Shared Assets Operations' (CSAO) Chester Secondary railroad line and PA 291 (Bartram Avenue).

The road comes to an interchange connecting to eastbound I-76 (Schuylkill Expressway), which leads to the Walt Whitman Bridge over the Delaware River, and Packer Avenue.

From here, I-95 curves to the northeast and passes near urban residential and commercial areas in the Fishtown neighborhood, coming to an interchange that serves Girard, Lehigh, and Delaware avenues.

I-95 passes under railroad tracks carrying NJ Transit's Atlantic City Line and CSAO's Delair Branch and crosses Frankford Creek as it comes to a stack interchange serving the Betsy Ross Bridge, which crosses the Delaware River and connects to the Route 90 freeway in New Jersey, and Aramingo Avenue.

After this interchange, the freeway narrows to six lanes and passes between residential areas to the northwest and Amtrak's Northeast Corridor to the southeast.

[4][6] Upon crossing Poquessing Creek, I-95 enters Bensalem Township in Bucks County and continues northeast parallel to the Amtrak line past suburban residential areas and some commercial development in the community of Andalusia.

I-95 reaches a diamond interchange with the eastern terminus of PA 132 at Street Road before the Amtrak line splits to the east and the highway comes to a bridge over US 13 with no access.

The freeway passes near wooded residential neighborhoods before it crosses Neshaminy Creek, at which point it heads into Bristol Township.

State highway officials reached a compromise by opting for an alternative depressed design with an overhead concrete deck connecting Center City to a planned redeveloped waterfront today known as Penn's Landing.

By 1979, the entire length of the freeway was open to traffic with the exception of a four-mile (6.4 km) segment near Philadelphia International Airport.

[3][8] Completion of the final section of the highway faced considerable difficulty, as the road was to be built on a layer of clay separating the city's water supply from the output of its sewage treatment plant.

[3][8] On March 13, 1996, a pile of tires that were illegally stored underneath I-95 in the Port Richmond neighborhood of Philadelphia caught fire.

The new ramps eliminated the traffic signal and stop intersections previously encountered by northbound I-95 motorists who had to use PA 291 to the airport.

Also under the project, PennDOT resurfaced I-95 between PA 420 and Island Avenue and built a truck enforcement and park-and-ride lot.

[13] On March 18, 2008, two miles (3.2 km) of I-95 within Philadelphia were closed when PennDOT discovered large cracks in a support column underneath the highway.

PennDOT worked quickly to stiffen the support beams to allow the road to be raised off the column, using 16 jacks, early on March 20.

In order to remedy this and also provide a continuous route for I-95, eliminating the gap in New Jersey caused by the cancellation of the Somerset Freeway, a high-speed interchange between the two roads was built.

[22][23] On June 11, 2023, a gasoline tanker crashed and caught fire underneath a bridge along I-95 at the PA 73 interchange in Northeast Philadelphia, kiling the driver.

Governor Josh Shapiro issued a disaster declaration on June 12, 2023, in order to allow for federal funds to be used for repairs.

Governor Shapiro, Philadelphia Mayor Jim Kenney, and PennDOT secretary Mike Carroll attended a ceremony marking the reopening of the highway.

Already, Richmond Street was widened and had new curbs, sidewalks, and traffic signals installed and trees planted, which, along with other improvements, cost $32.1 million.

[37] On December 31, 2015, Philadelphia Mayor Michael Nutter announced that a $10-million (equivalent to $12.6 million in 2023[11]) study funded by state and federal money would consider placing I-95 in a tunnel in the area around Penn's Landing.