Interstate 78 (I-78) is an east–west Interstate Highway in the Northeastern United States that runs 144 miles (232 km) from I-81 northeast of Harrisburg, Pennsylvania, through Allentown to western and North Jersey, terminating at the Holland Tunnel entrance to Lower Manhattan in New York City.

I-78 links ports in New York City and North Jersey to points west, including the Lehigh Valley, the third-largest metropolitan region of Pennsylvania.

I-78 begins at a directional T interchange with I-81 in Union Township, about 25 miles (40 km) northeast of Harrisburg.

[6] Approximately six miles (9.7 km) east, there is an interchange between PA 412 and I-78 in Hellertown, serving Bethlehem and Lehigh University.

The final exit on I-78 in Pennsylvania is Morgan Hill Road, which accesses PA 611 and Easton.

[7] The road begins by running parallel with County Route 642 (CR 642) in the town of Alpha.

At exit 41, I-78 enters Union County[8] and then passes through the Watchung Reservation, where land bridges cross over the highway to allow for the safe passage of wildlife.

Route 139 runs concurrently with I-78 along a one-way pair of surface streets as it approaches the Holland Tunnel and enters New York state.

The route was planned to run east and north through New York City to end at I-95 in the Bronx, but sections of the planned route, including the Lower Manhattan Expressway, were canceled.

In New York City, I-78 continues through the egress-only roundabout known as the Saint John's Rotary.

Under original plans, I-78 was to cross Manhattan as the Lower Manhattan Expressway onto the Williamsburg Bridge and then beyond I-278 on Bushwick Expressway through Brooklyn into Queens near the John F. Kennedy International Airport.

Under the plans, east of the airport, I-78 would have turned north on the Clearview Expressway, built north of Hillside Avenue in Queens and now I-295, run across the Throgs Neck Bridge, and forked into two spurs, ending at I-95 via the Throgs Neck Expressway, which is now I-695 and the Bruckner Interchange via the Cross Bronx Expressway, which is now part of I-295.

In the Lehigh Valley region of eastern Pennsylvania, PA 378, which exits in downtown Bethlehem was once I-378 but was predesignated as a state route after I-78 was rerouted to a new southerly alignment.