Fortune Gallo, an opera impresario who managed the touring San Carlo Opera Company, commissioned the house. It opened as the Gallo Opera House in November 1927, with the San Carlo troupe singing La bohème. Plays followed, and in 1928 Rainbow, a musical by Laurence Stallings and Oscar Hammerstein II, lasted less than a month. The venture soon failed; after a foreclosure sale in December 1929, the house reopened in 1930 as the New Yorker Theatre.
During the Depression the room turned into the Casino de Paree nightclub, with revues by Billy Rose, and from 1937 a WPA stage for opera and concerts. Medicine Show, in April 1940, was its last Broadway production for almost six decades.
CBS took a lease in August 1942, first for radio and from 1949 as television Studio 52. A subway power substation next door caused so much magnetic interference that the network needed shielded cameras. Audiences watched What's My Line? and Password being taped here; the soap opera Love of Life was the last to leave, in 1975.
The nightclub run by Steve Rubell and Ian Schrager opened on April 26, 1977. Celebrity guests, lavish parties and a door that turned many hopefuls away kept it in the gossip columns until both owners pleaded guilty to tax evasion and went to prison in early 1980. Later tenants included the Ritz rock club, and Allied Partners bought the property at auction in 1994.
Broadway returned almost by accident. In July 1998 a construction hoist collapsed at 4 Times Square, cutting off Henry Miller's Theatre, home of Roundabout's revival of Cabaret. The production moved here that November and stayed until January 2004, reaching 2,377 performances across both houses. Later seasons brought Assassins in 2004, a return of Cabaret in 2014, Sweat and Kiss Me, Kate.
The Landmarks Preservation Commission studied the building in the 1980s but did not designate it, so Studio 54 is not an official landmark. In May 2026 Roundabout launched a capital campaign that includes the first full overhaul of the theater in about a century; in the summer of 2026 the plan was still in the city's land-use review.