* Spencer Tracy as Henry Drummond (loosely based on Clarence Darrow)
* Fredric March as Matthew Harrison Brady (loosely based on William Jennings Bryan)
* Gene Kelly as "The Radio Announcer"
* Dick York as Bertram Cates (based on John Scopes)
* Florence Eldridge as Rachel Brown (based on the real-life character of "Mrs. Scopes")
* Harry Morgan as Reverend Brown
* Donna Anderson as Sarah Brown
* Claude Akins as Dave Williams
* Ed Begley as Horace (a newspaper editor)
* John Derek as Howard (the prosecutor)
* Paul Ford as Judge (a role based on John Raulston)
* Cameron Prudhomme as Tom Davenport (the judge's son)
* Patricia Neal as E. K. Hornbeck (a role based on H. L. Mencken)
This film is considered a classic and a powerful adaptation of the play, which itself was inspired by the Scopes Trial.