The play was first produced at the Royal Court Theatre in London in 1905 by J.E. Vedrenne and Harley Granville-Barker. Barker also played Cusins, alongside Louis Calvert, Clare Greet, Edmund Gwenn, Oswald Yorke and Annie Russell.
In the summer of 1988, the Chichester Festival Theatre presented a production with Donald Sinden as Andrew Undershaft, Anna Carteret as Barbara and Marc Sinden as Stephen Undershaft, directed by Christopher Morahan.
A production from 26 February to 3 July 2008 at the National Theatre featured Simon Russell Beale as Andrew Undershaft, Hayley Atwell as Barbara, Clare Higgins as Lady Britomart, Paul Ready as Cusins and Jessica Gunning as Sarah Undershaft.
The play first opened on Broadway at the Playhouse Theatre on December 9, 1915. There have been four Broadway revivals, in 1928 at the Guild Theatre, 1956 at the Martin Beck Theatre and then the Morosco Theatre starring Glynis Johns, Cornelia Otis Skinner, Eli Wallach, Burgess Meredith, and Charles Laughton, who also directed, in 1980 at the Circle in the Square Theatre, and 2001 at the American Airlines Theatre, with Cherry Jones in the title role.
The 1956 revival received the Tony Award for Best Stage Technician (Howard McDonald). It was nominated for Best Scenic Design (Donald Oenslager) and Best Costume Design (Dorothy Jenkins).
The 1980 revival received a Tony nomination for Reproduction (Play or Musical). (Theodore Mann: Artistic Director; Paul Libin: Managing Director).
The actor who played Andrew Undershaft in the 2001 revival, David Warner, received the Theatre World Award.
Major Barbara was revived in a production at the Abbey Theatre, Dublin from 21 July 2013. Annabelle Comyn directed; Clare Dunne played Barbara, Marty Rea Adolphus Cusins, Paul McGann Andrew Undershaft, Eleanor Methven Lady Britomart. 
A film adaptation of 1941 was produced by Gabriel Pascal, and starred Wendy Hiller, Rex Harrison and Robert Morley.
In Season 3 of HBO series Girls by Lena Dunham, a production of Major Barbara on Broadway forms the backdrop of lead character Hannah's relationship with her boyfriend Adam.
Caedmon Records released a 4-LP recording of the play in 1965 (TRS 319 S) directed by Howard Sackler with Warren Mitchell as Bill Walker, Maggie Smith as Barbara, Alec McCowen as Cusins, Celia Johnson as Lady Britomart and Robert Morley as Undershaft.
The L.A. Theatre Works has released an adaptation of the play in 2008 (ISBN 978-1-58081-381-5) with Roger Rees as Undershaft and Kate Burton as Lady Britomart.