The 50th Street station was constructed for the Interborough Rapid Transit Company (IRT) as part of the city's first subway line, which was approved in 1900.

[4]: 21  However, development of what would become the city's first subway line did not start until 1894, when the New York State Legislature passed 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.

[4]: 161 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,[6] under which it would construct the subway and maintain a 50-year operating lease from the opening of the line.

[5]: 4  Belmont incorporated the Interborough Rapid Transit Company (IRT) in April 1902 to operate the subway.

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

[10]: 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.

The original subway north of Times Square thus became part of the Broadway–Seventh Avenue Line, and all local trains were sent to South Ferry.

[35][36] In early 2024, a pizzeria opened next to the station's southbound platform, adjacent to an existing coffee shop and cocktail bar.

[21] As with other stations built as part of the original IRT, each platform consists of 3-inch-thick (7.6 cm) concrete slabs, beneath which are drainage basins.

Additional columns between the tracks, placed atop the transverse arches, support the jack-arched concrete station roofs.

[44]: 10  Most of the original tile plaques at this station were removed during remodeling, replaced by much simpler blue, green, and red mosaics with printed letters.

The station contains Liliana Porter's artwork Alice, The Way Out, a series of mosaics installed in 1994 as part of the MTA Arts & Design program.

According to former MTA Arts & Design director Sandra Bloodworth, "You see Alice pulling the curtain back in one of the images, and you have the theaters above ground.

[47] The southbound platform has an exit to an underground shopping arcade on the south side of 50th Street west of Broadway, where the "Nothing Really Matters" bar opened in 2022.