Inherit the Wind opened with actors Paul Muni, Ed Begley, and Tony Randall produced and directed by Herman Shumlin on January 10, 1955. It debuted at Broadway's National Theatre on April 21, 1955. It played on Broadway until June 22, 1957, where it closed after 806 performances. It was revived on Broadway twice: April 4, 1996 - May 12, 1996 and April 12, 2007 - July 8, 2007. The 1996 revival starred George C. Scott (who played Brady in the later 1998 film version) as Drummond and Charles Durning as Brady. In April, Scott had to leave the show mid-performance due to ill health and was replaced by the show's producer, Tony Randall for that day. Randall played the Wednesday matinees for Scott from that point on. His illness finally led to the revival's closure. Christopher Plummer and Brian Dennehy starred in the 2007 revival.
In the 1990s Jason Miller and Malachy McCourt starred in the Philadelphia production that broke that city's long run records.
In 2006 several scenes were translated in Italian for the first time by Luca Giberti for a series of Darwin-themed readings.
Kevin Spacey (Henry Drummond) and David Troughton (Matthew Harrison Brady) starred in a 2009 revival at The Old Vic in London.