The road crosses the Watchung Mountains, widening into a local–express lane configuration at Route 24 as it continues through urban areas to Newark.

[2][4] The freeway makes a turn to the east as it briefly passes through a corner of Alpha before coming back into Pohatcong Township.

I-78/US 22 continue east through Greenwich Township, coming to a westbound exit and eastbound entrance with South Main Street (CR 637).

[5] The freeway turns east again and enters Union Township, coming to an interchange with Pattenburg Road (CR 614) and Route 173.

[2] At the next interchange near the community of Annandale, US 22 splits from I-78 onto a four-lane surface highway, heading closely to the south of that route.

[2][4] Immediately after the split, I-78 passes over NJ Transit's Raritan Valley Line and runs through rural areas with increasing suburban development.

The freeway runs through Lebanon, where an exit for Cokesbury Road (CR 639) provides access to the town and the Round Valley Recreation Area.

[2] After crossing the Lamington River, I-78 comes into Bedminster, Somerset County, continuing east through more woods and farms with some suburban residential areas.

[2] The road enters wooded suburban areas and crosses the Second Watchung Mountain, running through a corner of Bridgewater, where there is a westbound scenic overlook, before coming into Bernards Township.

[2][4] The eastbound direction narrows back to three lanes before the interchange with Martinsville Road (CR 525), at which point the freeway crosses into Warren.

There is an eastbound exit and westbound entrance with Glenside Avenue (CR 527) as it heads away from the Watchung Reservation and into more suburban surroundings.

Before Route 124, I-78 briefly runs east through Millburn in Essex County and Springfield again before entering Union at the interchange.

[4] In Hillside, I-78 passes under Conrail Shared Assets Operations' Irvington Industrial Track line and has an eastbound exit and westbound entrance to Winans Avenue.

[2] I-78 here becomes a four-lane highway, heading over the New Jersey Turnpike and Conrail Shared Assets Operations' Chemical Coast Secondary and Corbin Street Lead lines before passing by the Port Newark–Elizabeth Marine Terminal.

From here, the freeway turns northeast on an elevated alignment and passes industrial areas of Jersey City, with Conrail Shared Assets Operations' National Docks Branch line parallel to the northwest.

[2][4] Continuing north, the road passes over the Hudson–Bergen Light Rail line before there is an exit for Columbus Drive and Montgomery Street.

I-78 heads down to surface level and passes over Conrail Shared Assets Operations' National Docks Branch line twice before it merges with Route 139.

The 8.2-mile (13.2 km) long expressway was opened in 1956 to provide access from the New Jersey Turnpike mainline to the Holland Tunnel.

[15] In July 1963, New Jersey Governor Richard J. Hughes approved a plan to build I-78 through the city of Newark at a cost of $205 million (equivalent to $1.56 billion in 2023[16]).

The section from Drift Road/Dale Road to Route 24 (exit 48) in Springfield was delayed because of environmental impacts to the Watchung Reservation.

In order to mitigate opposition to the original plan, that was shifted closer to the northern edge of the Reservation, which required extensive cuts into the Second Watchung Mountain.

Extra land was added to the Nikesite Road overpass and a separate elevated wildlife crossing was built to allow for animal migration.

The road was also designed to use a narrower right-of-way with no median strip and just a jersey barrier dividing the highway, to minimize the amount of rock to be removed.

[20] A section of I-78 in Newark was closed off in August 1989 when a debris pile under a bridge caught fire and damaged the elevated highway.

[21] The westernmost section of I-78 in New Jersey opened in November 1989 after a more northerly alignment along present day US 22 through Phillipsburg was rejected due to community opposition.

[23] The additional length of roadway that resulted from this rerouting is the reason exit numbers 3 through 52 (which were assigned before this westernmost section opened) are mismatched by approximately one mile (1.6 km) when compared to their corresponding milemarker.

Construction began in June 2008, with the ramp from the northbound Garden State Parkway to westbound I-78 being completed in September 2009.