Located at the intersection of Second Avenue and 72nd Street, in the Lenox Hill section of the Upper East Side in Manhattan, it opened on January 1, 2017.

The station was not originally proposed as part of the Program for Action in 1968, but a later revision to that plan entailed building a Second Avenue Subway with one of its stops located at 72nd Street.

The station opened on January 1, 2017, with provisions to extend the line south to Houston Street in Phase 3.

Since opening, the presence of the Second Avenue Subway's three Phase 1 stations has improved real estate prices along the corridor.

The artwork at 72nd Street is Perfect Strangers, a set of portrait mosaics by artist and photographer Vik Muniz.

The Second Avenue Line was originally proposed in 1919 as part of a massive expansion of what would become the Independent Subway System (IND).

[12] As part of the New York City Transit Authority's 1968 Program for Action, the construction of the full-length Second Avenue Subway was proposed.

[7]: 220 All Second Avenue Subway stations built under the Program for Action would have included escalators, high intensity lighting, improved audio systems, platform edge strips, and non-slip floors to accommodate the needs of the elderly and people with disabilities, but no elevators.

[16] The stations were to be made with brick walls and pavers alongside stainless steel, and would have relatively small dimensions, with 10-foot (3.0 m) mezzanine ceilings.

[17]: 110 A combination of Federal and State funding was obtained, and despite the controversy over the number of stops and route, a groundbreaking ceremony was held on October 27, 1972, at Second Avenue and 103rd Street.

[15][18][19] Although work on the 72nd Street station never commenced, three short segments of tunnel in East Harlem and Chinatown were built.

[26][27][28] The line's first phase, the "first major expansion" to the New York City Subway in more than a half-century,[29] included three stations in total (at 72nd, 86th, and 96th Streets), which collectively cost $4.45 to $4.5 billion.

[33] Due to cost increases for construction materials and diesel fuel affecting the prices of contracts not yet signed, the MTA announced in June 2008 that certain features of the Second Avenue Subway would be simplified to save money.

One set of changes, which significantly reduced the footprint of the subway in the vicinity of 72nd Street, was the alteration of the 72nd Street station from a three-track, two-platform design to a two-track, single island platform design, paired with a simplification of the connection to the Broadway Line spur.

[34][35] Supplemental environmental impact studies covering the changes for the 72nd Street station was completed in June 2009.

[43] Nearly two weeks later, on August 21, 2012, an uncontrolled blast for the Second Avenue Subway station at 72nd Street was done incorrectly,[44] causing a large explosion that sent debris into the air and broke windows of buildings in the area and damaged nearby sidewalks.

[71] Current plans do not call for it to be used by regular service, but instead to be used for non-revenue moves, and to provide a connection to the Jamaica Yard maintenance depot.

[80] As with other stations on the first phase of the Second Avenue Subway, it was designed and engineered by a joint venture of Arup and AECOM.

[86] According to an internal study prepared for the MTA in 2020, the 72nd Street station could theoretically accommodate half-height platform edge doors.

Full-height platform screen doors would be possible but would necessitate the installation of structural bracing and relocation of several mechanical systems.

[97][95] A married same-sex couple is also depicted, marking the first permanent, non-political LGBT art in New York City.

[102] One building at the northwest corner of Second Avenue and 72nd Street contains both ancillary equipment and a station entrance.

Due to vocal community opposition, the MTA non-publicly revised plans for the subway entrance in fall 2007, relocating the planned entrance to the southeast corner of Second Avenue and 72nd Street[107] Two years later, in 2009, a Finding Of No Significant Impact by the Federal Transit Administration found that a proposed entrance at the northeast corner of Second Avenue and 72nd Street was unfeasible, as was the proposed single sidewalk elevator at the southeast corner.

[108]: 3  The site for the sidewalk elevator on the southeast corner turned out to be located close to a high-pressure steam main that was 48 inches (120 cm) in diameter.

With the New York City Department of Transportation planning a bike lane along the east side of Second Avenue after construction is finished, the MTA could widen the sidewalk to make room for the entrances without ultimately disrupting traffic flow.