Builders Irwin and Henry Chanin, newcomers to show business, made the Biltmore their second Broadway theater, after the 46th Street Theatre (now the Richard Rodgers), and the first on the north side of West 47th Street, then a mostly residential block. The curtain first rose on December 7, 1925, on Owen Davis's Easy Come Easy Go.
The Chanins lost the building in the Depression. The Federal Theatre Project used the stage next, and in 1936 Warner Bros. bought it for George Abbott's productions, starting with the hit Brother Rat, and The Heiress premiered here in 1947. From 1952 to 1961, CBS used it as a radio and television studio.
Producer David Cogan brought plays back in 1961. Neil Simon's Barefoot in the Park, with Robert Redford and Elizabeth Ashley, opened in October 1963 and stayed until 1967, about 1,530 performances; the rock musical Hair followed in 1968 and ran into 1972.
On November 10, 1987, the Landmarks Preservation Commission protected the auditorium interior, though not the facade. A month later an arson fire damaged the stage and seats, and the dark house decayed under a series of owners, including the Nederlander Organization and Stewart F. Lane from 1993.
MTC began restoring it in December 2001. The theater reopened on November 6, 2003, with Richard Greenberg's The Violet Hour, was listed on the National Register of Historic Places in 2004, took its new name on September 4, 2008, and became MTC property the next month.
Later productions include David Lindsay-Abaire's Rabbit Hole (2006), which won the 2007 Pulitzer Prize for Drama, and two winners of the Tony Award for Best Revival of a Play: August Wilson's Jitney (2017) and Jonathan Spector's Eureka Day (2024).