The building originated as the Notre Dame Hall in 1953, replacing an earlier building that had been destroyed by World War II bombing. It was used as a French cultural centre for a time. It became a popular music venue in the 1960s under the name Cavern in the Town, regularly hosting beat music group The Small Faces. It was renamed Notre Dame Hall in the 1970s and presented The Rolling Stones and The Who, but specialised in punk music, hosting such acts as The Sex Pistols. In 1979, The Clash previewed material from London Calling here shortly before recording the album. The hall continued as a live music venue and dance hall, hosting such acts as Tommy Emmanuel, John Mayall, Cleo Laine, David McAlmont, Ruby Turner and Tony Christie. In 2001, it was converted to a theatre and named The Venue.

Among the theatre's famous productions have included the world premiere of the Boy George musical Taboo, which played a highly successful run in 2002 before transferring to Broadway, Round the Horne (2003) and two seasons of the Australian comedy The Vegemite Tales in 2007 and 2008. After this, the theatre was then named Leicester Square Theatre. American comedian Joan Rivers made her acting debut in August 2008 with her play Joan Rivers: A Work in Progress by a Life in Progress, which played a total of 75 performances to celebrate her birthday. A musical based on the comic strip Alex, by Charles Peattie and Russell Taylor, starring Robert Bathurst, finished the year 2008. Frisky & Mannish's School of Pop ran at the theatre in 2009. Wilfredo: Erecto! by Matt Roper, played in 2011, and An Evening with Joan Collins ran from 2011 to 2012. Bill Bailey, Rosanne Barr, Sandra Bernhard, Jo Brand, Doc Brown, Bill Burr, Julian Clary, Greg Davies, Macy Gray, Richard Herring, Russell Howard, Reginald D Hunter, Stewart Lee, Mark Little, Demetri Martin, Jerry Sadowitz, Miranda Sings, Tom Stade, Doug Stanhope, Ricky Tomlinson, and Tim Vine have also performed at the Leicester Square Theatre.

The theatre is owned and managed by artistic director Martin Witts.