The cinema was first known as the Regal, opening on 29 November 1928 with Al Jolson in The Singing Fool. A 100-foot (30 m) high facade was constructed in Portland stone. The auditorium was a riot of romanesque motifs and faux-decor, owing much to the atmospheric style of the USA. Structured in traditional circle and stalls, the cinema was a notable addition to the West End. It was also fitted with a Christie organ - the largest theatre organ ever built outside the United States fitted with 2,514 pipes, a 32-note carillon (the only real organ-operated carillon in the United Kingdom) and a wide variety of special sound effects to accompany the films.

Within six months of opening, the cinema was taken over by ABC Cinemas, who operated it until early January 1945. It was then taken over by Odeon Cinemas. It was refurbished by the new owners, but shortly before re-opening it was damaged by one of the last V-1 flying bombs to hit London. So it remained closed until September 1945, when it was re-opened as the Odeon Marble Arch and continued as a first-run house.

By the early 1960s its interior was decidedly faded and neglected. Film-runs had by this point declined to minor circuit pictures or even dubbed foreign films: insufficient to fill its large house. So, on 22 March 1964 it closed with The Long Ships, was demolished and replaced by an office block and a new modern cinema, with the architect being T.P. Bennett and Son, capable of playing the new widescreen formats. The new cinema, built above the Marble Arch tube station, required elaborate structural shock absorbers to prevent vibrations from the passing trains from disturbing the film projection.

Opening in 1967, the Odeon was the largest cinema constructed in the post-war years. The cinema was constructed to showcase films in the various 70mm processes, in particular Dimension 150, as well as conventional 35mm films, allowing for considerable spectacle. Presentations included: Far from the Madding Crowd, A Bridge Too Far, Aliens, Die Hard, Return of the Jedi, Lawrence of Arabia. The screen was the largest in the country.

In January 1997, the cinema reopened as a 5 screen multiplex, converted within the existing space.

In March 2011 Odeon Marble Arch had its 35mm projectors and CP65 sound processors removed and went fully digital in all five screens using NEC digital projectors with Doremi servers, Only screen one retained its Victoria 8 35mm projector and Cinemecanica non-rewind system alongside the Digital system for the occasional 35mm shows.

On 8 May 2016, the Odeon Marble Arch within the 1967 building closed its doors for the final time, and was demolished later that year.