The name was one used for many different theatres and music halls, of which the London Hippodrome is one of only a few survivors. Hippodrome is an old word referring to places of entertainment where horse races were staged.

The London Hippodrome was first opened in 1900 as a venue for circus and variety performances. The first show ever given was a music hall revue entitled "Giddy Ostend" with Little Tich and (in one of his first roles) Charlie Chaplin. Entry to the venue was through a bar, dressed as a ship’s saloon and the performance space featured both a proscenium stage and an arena that sank into a 230 ft, 100,000 gallon water tank (400 ton, when full) for aquatic spectacles. Shows included equestrian acts, elephants and polar bears, and acrobats would dive from a Minstrel Gallery above a sliding roof, in the centre of the proscenium arch. The auditorium featured cantilevered galleries, removing the columns that often obstructed views in London theatres, the whole was covered by a painted glass retractable roof, that could be illuminated at night.

In 1909, it was reconstructed as a music-hall and variety theatre with 1340 seats in stalls, mezzanine, gallery, and upper gallery levels. It was here that Tchaikovsky’s Swan Lake received its English première by the Ballets Russes in 1910. The Albert de Courville revues were performed here from December 1912.

In 1919, the Hippodrome hosted the first official jazz gig in the United Kingdom, by the Original Dixieland Jazz Band.

Its reputation was for revue and musical comedy, among them The Five O’Clock Girl, the West End production of Vincent Youmans’ hit Broadway musical Hit The Deck (1928) and also Mr. Cinders, both in 1929; Ivor Novello’s Perchance to Dream in 1945 with Margaret Rutherford; and the revue High Spirits in 1953 with Cyril Ritchard and Diana Churchill. Julie Andrews made her stage debut here at the age of 12.

In 1958, the original interior was demolished and the London Hippodrome was converted into the nightclub, "The Talk of the Town" by Bernard Delfont, featuring many of the popular artistes of the time - Diana Ross & The Supremes, Judy Garland, Shirley Bassey, Frank Sinatra and Sammy Davis Jr. all appeared here. This form of entertainment, in its turn fell out of public favour and the venue closed in 1982.

Renovated yet again, the building was reopened as a nightclub/restaurant called "The London Hippodrome" by nightclub tycoon Peter Stringfellow in 1983. Some years later, Stringfellow sold it to a chain company called European Leisure.

In April 2004 the Hippodrome was transformed into "Cirque at the Hippodrome". It was revealed in October 2005 that the club had lost its public drinks licence and would no longer be able to serve alcohol. In December 2005, the club was eventually forced to close.

In January 2006 entrepreneur Charmaine Haig took over the lease of the Hippodrome building on a short term before a casino licence application could be secured for future use.

In 2008 Haig and her business partner acquired a theatre licence for the venue and subsequently turned the venue back into a theatre.

In 2009, the lease on the Hippodrome was acquired by Jimmy and Simon Thomas, who began an extensive restoration programme taking the Hippodrome back to Matcham’s original designs for use as a casino and entertainment venue. The Hippodrome Casino was opened on 13 July 2012 by then Mayor of London Boris Johnson.