[5]: 21  However, development of what would become the city's first subway line did not start until 1894, when the New York State Legislature authorized the Rapid Transit Act.

It called for a subway line from New York City Hall in Lower Manhattan to the Upper West Side, where two branches would lead north into the Bronx.

[5]: 148  The Rapid Transit Construction Company, organized by John B. McDonald and funded by August Belmont Jr., signed the initial Contract 1 with the Rapid Transit Commission in February 1900,[7] in which it would construct the subway and maintain a 50-year operating lease from the opening of the line.

[5]: 182 The IRT's East Side Branch now the Lenox Avenue Line was largely constructed as part of Section 8, built by Farrell & Hopper.

[7][8]: 252  The excavation was relatively easy because the subway was under one side of Lenox Avenue and, as such, there were no street railway tracks to work around.

[8]: 252–253  At Lenox Avenue and 110th Street, a 6.5-foot (200 cm) diameter circular brick sewer, draining 124 acres (50 ha) of the west side of Manhattan, was intersected by the subway.

[16] In April 1907, IRT officials decided to create a concrete drain beneath the Lenox Avenue Line tunnel, during which time trains in both directions ran on the southbound track during late nights.

[17] In Fiscal Year 1910, the bottom of the tunnel at the south end of the 116th Street station was rebuilt to prevent leaking.

[20] To address overcrowding, in 1909, the New York Public Service Commission proposed lengthening platforms at stations along the original IRT subway.

[21]: 168  As part of a modification to the IRT's construction contracts, made on January 18, 1910, the company was to lengthen station platforms to accommodate ten-car express and six-car local trains.

This was done to correct a major water problem that had existed for many years due to the continued presence of the Harlem Creek and other underground streams, which caused extensive flooding, water damage, and seepage problems that occasionally contributed to severe service disruptions.

[38] On March 27, 2020, a northbound 2 train caught fire while approaching Central Park North–110th Street, the southernmost station on the line.

Subway service on the Lenox Avenue Line resumed on March 30, bypassing the Central Park North station until it reopened on April 6.