The road runs 35.62 miles (57.32 km) from US Route 1/9 (US 1/9) in Linden, New Jersey, northeast to the Bruckner Interchange in the New York City borough of the Bronx.

I-78 was also planned to extend east beyond I-278 to John F. Kennedy International Airport, and then curve northward on the Clearview Expressway, ending at the Bruckner Interchange in the Bronx.

[4] After Todt Hill Road and Slosson Avenue, I-278 runs through a wooded area where it comes to an incomplete interchange that was to be the northern terminus of the Richmond Parkway.

[2][3] The Gowanus Expressway turns northeast again at the interchange with Belt Parkway, and it continues along an elevated alignment above Third Avenue, running through urban residential and commercial areas.

[13][14] After the exit for the Brooklyn–Battery Tunnel, I-278 heads north onto the six-lane BQE, passing through urban neighborhoods near Downtown Brooklyn on a depressed alignment.

Upon entering Queens, the BQE runs north between residential neighborhoods to the east and Calvary Cemetery to the west before coming to an interchange with the LIE (I-495).

[2][3] At this point, I-278 becomes city-maintained again and passes under the Long Island Rail Road's Main Line as it continues into a depressed alignment.

A short distance past Northern Boulevard (NY 25A), the freeway splits into east and west segments with four lanes each that respectively merge into the Grand Central Parkway east- and westbound.

[17] I-278 turns west to run along the eight-lane state-maintained Grand Central Parkway, with Astoria Boulevard (and Hoyt Avenue later on) serving as a frontage road.

[3][16] The road runs along a depressed alignment, passing under Amtrak's Northeast Corridor, then the New York City Subway's BMT Astoria Line at 31st Street.

[3] The Grand Central Parkway overlap ends at the interchange with 31st Street, and I-278 continues northwest along the tolled, eight-lane Robert F. Kennedy Bridge, which passes over Astoria.

[2] Sheridan Boulevard (NY 895) splits from the eastbound direction of I-278 as the Bruckner Expressway makes a turn to the east into residential and commercial neighborhoods on a surface alignment, crossing the Bronx River on a drawbridge.

[22] Even though it was to run along an abandoned railroad right-of-way, it would traverse through dense development in Roselle Park, Kenilworth, and Union Township,[23] thereby making the project further disliked.

The earth removed from the cut in the hill was placed in a remote section of central Staten Island adjacent to Sea View Hospital and has since been nicknamed "Moses Mountain".

[5] The aborted section, from the expressway to Richmond Avenue, has become a part of the Staten Island Greenbelt, one of New York City's public parks.

Part of the trail system of the greenbelt was using the abandoned overpass bridge as pedestrian crossing of the expressway up until 2013, when it was dismantled for lane widening improvements.

[50] The viaduct's vertical steel supports show material missing due to rust,[51] but the federal government has stated that it is not in danger of collapse.

[61] The road in its entirety was completed on December 23, 1964 at a cost of $137 million (equivalent to $1.03 billion in 2023[25]), with the opening of a mile-long (1.6 km) underpass connecting Queens Boulevard with Roosevelt Avenue.

For a short time, the segment of highway between the Robert F. Kennedy and Williamsburg bridges was to be designated I-87 and continue north as the Major Deegan Expressway.

This option would have served as a bypass, with vehicles heading to Downtown Brooklyn, or the Manhattan and Williamsburg bridges using the triple cantilever structure, which would be tolled.

[79] The structure is supported by steel rods inside rebar, which is corroding due to the seeping of road salt into widening cracks.

[80][81] In late 2018, NYSDOT proposed rebuilding the double-decker, 1.5-mile (2.4 km) section of I-278 running under the Brooklyn Heights Promenade, which had deteriorated severely over the years.

[81] Because of sizable opposition to demolishing the promenade, mayor Bill de Blasio later stated that his administration was open to considering other ideas, including routing the expressway over Brooklyn Bridge Park.

[85] Hundreds of people, including Brooklyn Borough President Eric Adams and City Comptroller Scott Stringer, rallied on the promenade, calling for more public review.

In response, the Brooklyn Heights Association came up with an alternate plan, which called for the construction of a temporary bilevel roadway running besides the promenade on land including a parking lot.

[86] Support for reducing the size of or tearing down the BQE increased, with articles in New York and The Wall Street Journal calling for the removal of the highway.

[89] On March 13, 2019, Stringer issued a plan calling for converting the triple cantilever structure and the open cut in Cobble Hill into a truck-only highway between Hamilton Avenue in Carroll Gardens and the Brooklyn Bridge.

The report expected passenger vehicles to be diverted into the underused Brooklyn–Battery Tunnel, whose tolls might be lowered when congestion pricing in New York City was implemented.

[94] In late 2021, the section between Atlantic Avenue and the Brooklyn Bridge was reduced from three to two lanes per direction, a move that city officials said could prolong the viaduct's life by 20 years.

[98][99] NYCDOT formally presented the three plans to the public in February 2023,[100][101] and city officials began issuing summonses to overweight vehicles in August of that year.