Judy Garland was originally cast as Annie, as MGM bought the project specifically for her. She not only recorded the entire score and was fitted for every costume, she also filmed two production numbers. Due to a number of factors, including poor health and an inability to get along with director Busby Berkeley, she was eventually dismissed from the film. Betty Hutton, who had wanted the part from the beginning, was loaned out from Paramount to assume the role, with George Sidney taking over from Berkeley as director.
Frank Morgan was initially cast as Buffalo Bill. He recorded his lines for the song "There's No Business Like Show Business" and shot his brief appearance for Berkeley's version of the opening number. During the hiatus in production after Garland's dismissal, he passed away unexpectedly from a heart attack. Louis Calhern took over the role when production resumed with Betty Hutton.
Geraldine Wall was first slated to play Dolly Tate and appeared in the opening number opposite Morgan. For unexplained reasons, Benay Venuta was cast in her place when the film was restarted later in the year.