I-476 intersects many major roads, including I-76 (Schuylkill Expressway) in West Conshohocken, I-276 (Pennsylvania Turnpike) in Plymouth Meeting, U.S. Route 22 (US 22) near Allentown, and I-80 near Hickory Run State Park.

The portion of I-476 between I-95 and the Pennsylvania Turnpike (I-276) runs north–south through Delaware and Montgomery counties and is officially known as the Mid-County Expressway and the Veterans Memorial Highway, as well as by the nickname the "Blue Route".

[4] Heading north, the road passes under CSX's Philadelphia Subdivision rail line and has an interchange with MacDade Boulevard in Woodlyn, where it narrows to a four-lane parkway that runs parallel to the Crum Creek.

It winds through the western Philadelphia suburbs of Wallingford and Swarthmore, where I-476 passes under SEPTA's Media/Wawa Line and comes to a diamond interchange with Baltimore Pike just west of Springfield.

From here, the freeway crosses over SEPTA's light rail Media–Sharon Hill Line and continues north to Springfield, where it meets US 1 at a three-level diamond interchange.

The route continues through the Philadelphia suburbs, passing over CSX's Stony Creek Branch rail line, and reaches an interchange with PA 63 west of Lansdale that serves the North Penn Valley region.

[4] North of Allentown, the route crosses under Norfolk Southern's Catasauqua and Fogelsville Railroad line and runs through farmland with some development.

Continuing through mountainous areas, the route has ramps to the dual-access Hickory Run Service Plaza prior to coming to a diamond interchange with PA 903 in Penn Forest Township.

[4] The route continues through mountainous terrain, heading into Luzerne County at a crossing of the Lehigh River and coming to an interchange with PA 115 in Bear Creek that provides access to nearby Wilkes-Barre.

North of Scranton in Clarks Summit, the route crosses a valley on the 1,630-foot-long (500 m), 163-foot-high (50 m) John E. Fitzgerald Memorial Bridge,[10] passing over Norfolk Southern's Sunbury Line, US 6/US 11, and PA 407.

Past the bridge, I-476 comes to a hairpin curve and reaches a mainline all-electronic toll plaza before it ends at an interchange with connections to I-81, US 6, and US 11.

As of 2024[update], it costs a passenger vehicle $26.20 to travel the length of the Northeast Extension between Mid-County and Wyoming Valley using toll by plate and $12.80 using E-ZPass.

[17] The Pennsylvania Turnpike Commission (PTC) broadcasts current roadway, traffic, and weather conditions via highway advisory radio transmitters at each exit.

[19] The Northeast Extension of the Pennsylvania Turnpike has two service plazas at Allentown and Hickory Run, which are accessible by both northbound and southbound traffic.

[26] The road received its nickname from a 1958 location report indicating various proposed geographic configurations of an expressway through Delaware County with lines of various colors on a map.

The Radnor Gateway Enhancement Strategy was implemented to install large scale sculpture elements by artist William P. Reimann, most notably the stone griffin and cairn at exit 13.

[28] While the redesigned highway was largely well-received, the constriction to four lanes has led to bottleneck conditions in the area, and many communities that originally opposed the road have now called for its widening.

[29] The Philadelphia Inquirer dubbed I-476 "the most costly, most bitterly opposed highway in Pennsylvania history" due to the decades of opposition it garnered.

In the 2000s, the road underwent a rehabilitation project, including paving, bridge repair, and ramp maintenance of the entire length of the freeway between I-95 and the Pennsylvania Turnpike.

The first phase will add variable speed limits that can change based on weather and congestion, new ramp meters, and electronic signs.

[34][35] Groundbreaking for the Northeastern Extension occurred on March 25, 1954, in White Haven, with Governor John S. Fine and commission chair Thomas J. Evans present.

The Northeast Extension was planned to run from the mainline Pennsylvania Turnpike in Plymouth Meeting north to a temporary terminus at Scranton.

[36] In April 1954, $233 million (equivalent to $2.1 billion in 2023[22]) in bonds were issued to build the Northeastern Extension along with the Delaware River–Turnpike Toll Bridge on the mainline Pennsylvania Turnpike.

[52] That June, a losing bidder decided to challenge the turnpike commission, saying it violated female and minority contracting rules regarding the percentage of these employees that were used for the project.

[64] This extension resulted in I-476 surpassing the 120-mile (190 km) I-495 in Massachusetts as the longest auxiliary Interstate Highway,[65] though it could be contested for this title in the future by I-369 in Texas.

[71] On December 2, 2000, E-ZPass debuted along the Northeast Extension of the Pennsylvania Turnpike between the Mid-County Toll Plaza and Lehigh Valley Interchange.

[80] In November 2006, Governor Ed Rendell and former Pennsylvania House Speaker John Perzel suggested leasing the extension long-term to a private group to raise money to improve other infrastructure in the state.

On March 17, 2017, the PTC announced that it would begin removing the feedback signals as part of upgrading toll equipment because they do not conform to federal signage guidelines.

As done on the first project, the Lansdale–Quakertown segment was rebuilt in two sections, with a southern half started in late 2017, widening the road to six lanes with full shoulders.

[114][115] In late 2021, construction began to replace the functionally obsolete Hawk Falls Bridge that carries I-476 over Mud Run in Carbon County.