On 27 December 1904 the curtain rose on a Boxing Day pantomime that was not quite a pantomime. J.M. Barrie's Peter Pan, or The Boy Who Wouldn't Grow Up debuted at the Duke of York's that night. The flying effects were primitive by modern standards but astonished the audience. A small actress named Nina Boucicault played the title role, beginning a tradition of women playing Peter that has continued ever since. Tinker Bell was a darting spot of light. The first audience was asked to clap to save the fairy's life, and they did. The play returned to the Duke of York's almost every Christmas for years afterward. Barrie had written something that would outlive him by a century, premiered in a theatre that was already a decade old.

Four years before Peter Pan, in 1900, the Duke of York's hosted another play that would alter musical history. David Belasco's Madame Butterfly, a one-act tragedy about an American naval officer and a young Japanese woman, played the theatre that year. In the audience one evening was Giacomo Puccini. He did not understand much English but understood what was happening on stage. He took the story home to Italy and turned it into the opera that the world now knows, Madama Butterfly, which premiered in Milan in 1904. The seed had been planted in St Martin's Lane. The Duke of York's also staged Jerome K. Jerome's Miss Hobbs that same year and Go-Bang, one of the earliest musical comedies, back in 1894. The theatre had a talent for being where things began.

The Duke of York's was Grade II listed in September 1960, protecting its modest red-brick façade from redevelopment. In the late 1970s the freehold was purchased by Capital Radio, who closed it in 1979 for a comprehensive refurbishment. It reopened in February 1980 with Rose, starring Glenda Jackson, the Oscar-winning actress who would later become a Labour MP. ATG Entertainment bought the theatre in 1992, the same year a Royal Court production of Ariel Dorfman's Death and the Maiden transferred in to great success. From there on the theatre established a particular character: serious drama, intelligent revivals, transfers from the Royal Court. It would not chase the long musical runs that defined other West End venues. It would do plays, and it would do them well.

The roll call of recent productions reads like a survey of contemporary British acting. Michael Gambon in Beckett's Eh Joe in 2006, and in Pinter's No Man's Land in 2008. Jeremy Irons in Embers. Mark Rylance in Farinelli and the King in 2015. Ian McKellen in King Lear in 2018 and again in Mother Goose in 2022. Amy Adams in The Glass Menagerie in 2022. Andrew Scott playing every part in Vanya in 2023. Tom Holland playing Romeo in 2024 with the Jamie Lloyd Company. The theatre houses the offices of Sonia Friedman Productions, one of the most influential producing companies in London. The Rocky Horror Show celebrated its 21st anniversary here in 1995. The Duke of York's has remained, against all West End economic logic, a writer's and actor's house.

In 2021 the singers Rag'n'Bone Man and Pink filmed the music video for Anywhere Away From Here inside the empty theatre, COVID still hanging over London's stages. The video moves through the gilded auditorium and onto the bare boards, two voices in a space designed for hundreds of voices a night. The Duke of York's reopened later that year with The Ocean at the End of the Lane, adapted from Neil Gaiman's novel. As of 2026, Sheridan Smith is playing Alan Ayckbourn's Woman in Mind. The theatre has hosted Brie Larson as Elektra and Lily Collins in Barcelona. Walter Emden's red-brick auditorium on St Martin's Lane, built for an opera singer's vision in the 1890s, keeps finding new things to be. The play, as it has done since Peter Pan first flew, continues.