Babe Ruth missed several days of shooting and filming during the production because of his own illness.
In reality, Gary Cooper was decidedly not a fan of baseball and required extensive coaching in order to look even passable on a baseball diamond. In fact, he had never played the game before, even as a youth, and had never even seen a baseball game in person until he was hired for this film.
Samuel Goldwyn was initially reluctant about making the film as he believed that baseball movies were box office poison. He was persuaded to do it when he viewed footage of Gehrig's famous farewell speech.
When Samuel Goldwyn began looking for someone to play Lou Gehrig in this movie, he quizzed baseball writers. The Sporting News polled the fans, and their pick was Cleveland Indians pitcher Johnny Humphries because of the strong facial resemblance. Goodwyn considered the candidates, but instead chose seasoned actor Gary Cooper for the role.