The Duke of York’s Theatre opened in 1892, then named the Trafalgar Square Theatre, and was renamed to its current name in 1895 to honour the future King George V. The theatre has housed acclaimed productions since, such as King Lear, and playing host to many famous names, including Sir Ian McKellen, Orlando Bloom, Michael Gambon and Jeremy Irons.

The Duke of York's Theatre was built for Frank Wyatt and his wife, Violet Melnotte, who retained ownership of the theatre until her death in 1935.

The theatre's opening show was comic opera The Wedding Eve by Frédéric Toulmouche. One of the earliest musical comedies, Go-Bang, was a success at the theatre in 1894. In 1900, Jerome K. Jerome's Miss Hobbs was staged as well as David Belasco's Madame Butterfly, which was seen by Puccini, who later turned it into the famous opera. This was also the theatre where J. M. Barrie's Peter Pan, or The Boy Who Wouldn't Grow Up debuted on 27 December 1904. Many famous British actors have appeared here, including Basil Rathbone, who played Alfred de Musset in Madame Sand in June 1920, returning in November 1932 as the Unknown Gentleman in Tonight or Never.

The theatre was Grade II listed by English Heritage in September 1960. In the late 1970s the freehold of the theatre was purchased by Capital Radio and it closed in 1979 for refurbishment. It reopened in February 1980 and the first production under the patronage of Capital was Rose, starring Glenda Jackson. In 1991 comedian Pat Condell performed sketches at the theatre which were later released on DVD.

The Ambassador Theatre Group bought the theatre in 1992; this coincided with the successful Royal Court production of Ariel Dorfman's Death and the Maiden. A host of successes followed including the 21st anniversary performance of Richard O'Brien's The Rocky Horror Show and the Royal Court Classics Season in 1995.

The theatre is the London headquarters of the Ambassador Theatre Group, as well as the producing offices of their subsidiary Sonia Friedman Productions, whose revival of In Celebration starring Orlando Bloom played until 15 September 2007.