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.

One of the first films to have a pre-credits opening sequence.

Lon Chaney Jr. wore special shoes to play Lennie. These increased his height by six inches.

The two lead roles were hotly contested parts in Hollywood in 1939. It came as a great surprise to many in the industry when director Lewis Milestone opted for two relative unknowns.

The very first screen adaptation of a John Steinbeck novel.

Lewis Milestone himself was once an itinerant worker.

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.

Lon Chaney Jr.'s role as Lennie is believed to have caused him to become typecast as hulking but sympathetic monsters at Universal Studios.

The movie was produced by 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."

The name "Mae" was given to Curly's wife specifically for this film version. In the original novel,the original play, and in other film and television versions she is simply known as "Curly's Wife".

First movie for which Aaron Copland wrote a soundtrack.

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.

The November 20, 1959 episode of Twilight Zone "Time Enough at Last" which stars Burgess Meredith as Henry Bemis, ends with this closing narration by Rod Sterling: "The best laid plans of mice and men and Henry Bemis, the small man in the glasses who wanted nothing but time..." an obvious tip of the hat, nod, wink and smile to Meredith's previous role.

"Theater Guild on the Air" broadcast a 60 minute radio adaptation of the movie on May 8, 1949 with Burgess Meredith reprising his film role.

Leona Roberts as "Aunt Clara" is in studio records/casting call lists for this movie, but was not seen in the viewed print.

This film was first telecast in Los Angeles Sunday 11 July 1948 on KTLA (Channel 5), in Chicago Monday 6 December 1948 on WGN (Channel 9), in New York City Monday 1 February 1949 on WPIX (Channel 11), in Philadelphia Tuessday 5 July 1949 on WCAU (Channel 10), and in Cincinnati Monday 12 September 1949 on WCPO (Channel 7), as part of their series of three dozen Hal Roach feature film productions, originally theatrically released between 1931 and 1943, and now being syndicated for television broadcast by Regal Television Pictures.