The Horse Shoe Brewery had stood at the corner of Tottenham Court Road since 1764. After the 1814 flood it was rebuilt and continued operating for over a century. The Court Cinema replaced it in 1911. The Court Cinema gave way to the Dominion in 1928, designed by the brothers W and TR Milburn on a budget of £460,000. They built it Renaissance revival in style: pilasters framing the upper floors, a concave central section faced with Portland stone, a three-bay bow window topped by two gryphons. The gryphons disappeared, apparently in 1932, and the theatre's character shifted with the times. In 2014, during a fifteen-week closure after Queen's musical finished, the gryphons were finally restored to their roost above Tottenham Court Road.

The Dominion opened as a musical theatre but lasted less than a year in that incarnation. In February 1931 it hosted the London premiere of Charlie Chaplin's City Lights, with Chaplin himself in attendance to watch his silent masterpiece play to a London audience. The film was already an anachronism, silent in an industry that had moved to sound, but Chaplin had refused to make a talkie. By 1933, after the controlling company collapsed, the Dominion was sold to the Gaumont cinema chain. It would remain primarily a cinema for nearly fifty years. In 1937, John Logie Baird gave the first demonstration of his system for transmitting live television to cinemas over a landline, using the Dominion. By December that year his colour transmissions had become part of the theatre's variety shows.

In February 1958 the Dominion closed for renovations. Two Philips 70mm projectors were installed along with a forty-five-foot-wide screen and the Todd-AO widescreen system, the upper circle was sealed off to become offices, and on 21 April the film version of Rodgers and Hammerstein's South Pacific opened. It played for four years and twenty-two weeks, grossing $3.9 million, a run so long it became a London tourist destination in its own right. In 1963 Elizabeth Taylor came in person for the European opening of Cleopatra, which played for almost two years. Then, from 29 March 1965 to 29 June 1968, the Dominion screened The Sound of Music continuously, the longest run of the film anywhere in the world. Three years and three months of Julie Andrews on a single Alpine screen.

On 14 May 2002 a musical opened at the Dominion that nobody quite expected to succeed. We Will Rock You used the songs of Queen, stitched together by British comedian Ben Elton into a story written with guitarist Brian May and drummer Roger Taylor. Critics were brutal. Audiences disagreed. The show was scheduled to close in October 2006 before a UK tour. Instead it kept running, and running, finally closing on 31 May 2014 after twelve years at the Dominion. In 2012, to mark the show's tenth anniversary, an area once devoted to Judy Garland memorabilia was converted into the Freddie Mercury Suite, displaying photographs from the singer's life. He had died in 1991, eleven years before his band's songs colonised this theatre. The walls outlasted him.

When We Will Rock You finally ended, the Dominion underwent its most extensive refurbishment. Both interior and exterior were restored. The gryphons came back. The backstage flying system was modernised. In 2017 a double-sided LED screen was unveiled on the façade, billed as the largest and highest-resolution exterior screen on any West End theatre. The Dominion has since hosted Evita, Bat Out of Hell, The Prince of Egypt for nearly two years, The Devil Wears Prada with music by Elton John, and a returning Grease. There is one more strange chapter. Since January 2005, Hillsong Church London has held its Sunday services in the auditorium. On weeknights the stage carries musicals; on Sunday mornings it carries sermons. The theatre on the brewery on the flood site has become whatever London needs it to be.