Originally produced by the Manhattan Theatre Club on 23 May 2000, it transferred to Broadway at the Walter Kerr Theatre on 24 October 2000. Directed by Daniel J. Sullivan, the production starred Mary-Louise Parker as Catherine, Larry Bryggman as Robert, Ben Shenkman as Hal, and Johanna Day as Claire. Later during the Broadway run, Jennifer Jason Leigh (September 13, 2001 to June 30, 2002) and Anne Heche took over the lead role. Josh Hamilton and Neil Patrick Harris subsequently played the role of Hal. Mary-Louise Parker won the Tony Award for her performance.
From March 13, 2013 to April 27, 2013, a production appeared at London's Menier Chocolate Factory. It featured Mariah Gale in the role of Catherine and Polly Findlay directed.
In April and May 2013, a new production by the Whitmore Eclectic Theater Group opened in Los Angeles at the Hayworth Theatre for a limited run. James Whitmore Jr., son of the award-winning iconic actor James Whitmore, stars and Aliah Whitmore, his daughter directed. A production in May 2013 opened at Carolina Actors Studio Theatre in Charlotte, North Carolina.
In September to October 2013, Proof was directed by Emily Mann at the McCarter Theater in Princeton, NJ.