Original plans were to name the venue Central Theatre. However, after lengthy debate, it was named The Queen's Theatre and a portrait of Queen Alexandra was hung in the foyer.
The first production at the Queen's Theatre was a comedy by Madeline Lucette Ryley called The Sugar Bowl. Although it was poorly received and ran for only 36 performances, the theatre received glowing reviews.
Through its history, the theatre has seen such talents as Peggy Ashcroft, Fred and Adele Astaire, Tallulah Bankhead, Kenneth Branagh, Noël Coward, Henry Daniell, Marlene Dietrich, Robert Donat, Edith Evans, Douglas Fairbanks, Jr., John Gielgud, Cedric Hardwicke, Jack Hawkins, Nigel Hawthorne, Celia Johnson, Jane Lapotaire, Alec Guinness, Rachel Kempson, Gertrude Lawrence, Robert Morley, Stephen Fry, Anthony Quayle, Basil Rathbone, Michael Redgrave, Miranda Richardson, Margaret Rutherford, Fiona Shaw, Nigel Havers, Maggie Smith, Sybil Thorndike, Nick Jonas,and Ramin Karimloo. Recent notable shows at the Queen's include the Tony Award winning musical Contact; Cyberjam, a production by the Emmy and Tony Award winning creators of Blast!; and The Taming of the Shrew.
In September 1940, a German bomb landed directly on the theatre, destroying the facade and lobby areas. The production at the time was Daphne du Maurier's Rebecca starring Celia Johnson, Owen Nares and Margaret Rutherford. The theatre remained closed until a £250,000 restoration was completed by Westwood Sons & Partners almost 20 years later. The auditorium retained its Edwardian decor while the lobbies and exterior were rebuilt in a modern style. The reconstructed theatre opened 8 July 1959 with John Gielgud's solo performance in Shakespeare speeches and sonnets, Ages of Man.
From April 2004 to July 2019, the theatre played host to Cameron Mackintosh's production of Les Misérables which transferred after 18 years at the nearby Palace Theatre. The musical celebrated its 20th anniversary at the venue on 8 October 2005 and overtook Cats as the longest running musical of all time a year later on 8 October 2006.
The theatre was Grade II listed by English Heritage in June 1972.
An extensive refurbishment was undertaken in the latter half of 2009 which improved public areas and increased capacity with new seating and boxes reinstated at dress circle level.
In 2019, Cameron Mackintosh announced that the original production of Les Misérables would close on 13 July 2019 while the theatre underwent a major restoration, but would return in a new production from 18 December 2019, when The Queen's Theatre would be renamed as The Sondheim Theatre in honour of composer and lyricist Stephen Sondheim.