Lon Chaney Jr. had played the role of "Lennie" in the Los Angeles stage production of "Of Mice and Men," and asked director Lewis Milestone for a screen test. Milestone was planning on casting Broderick Crawford in the role, but agreed to let Chaney feed lines to actresses testing for the part of "Mae." By the end of all the tests, Milestone had changed his mind, and cast Chaney in the part without a test of his own.
The play "Of Mice and Men" by John Steinbeck opened at the Music Box Theatre in New York on 23 November 1937 and closed in May 1938 after 277 performances. The opening night cast included Broderick Crawford (as Lenny), Wallace Ford (as George) and Will Geer (as Slim). Leigh Whipper (as Crooks) was the only member of the Broadway cast to appear in the film.
The movie was released by the production company of Hal Roach, producer of Stan Laurel and Oliver Hardy and "Our Gang" comedies. During one of Roach's last interviews, television talk-show host Tom Snyder complimented him on the film. Roach responded, "It could've used more laughs."
In the dinner sequence Mae, who expects to go to the movies later that evening, shows Curly a pair of theater tickets. Briefly glimpsed are the titles of the films she plans to see, Captain Fury (1939) and Zenobia (1939) both Hal Roach productions, the latter starring Oliver Hardy without Stan Laurel.