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Voice-over narration, spoken by Chill Wills as "the spirit of Chicago," is heard at the beginning and end of the film. Wills later appears in the story calling himself "Joe," but his character remains mysterious throughout the picture. End credits include a written dedication to the police and police departments of America, and an acknowledgment of the assistance and cooperation of the city of Chicago and its police department in making the film.
According to a March 1950 Los Angeles Daily News news item, Allan Dwan was originally assigned to direct City That Never Sleeps. Hollywood Reporter production charts list Tony Martinelli as film editor and Ed Crain, Sr., as soundman, although only Fred Allen, as film editor, and Dick Tyler and Howard Wilson, as soundmen, were listed onscreen. Portions of the film were shot on location in Chicago, according to Hollywood Reporter and Variety reviews. City That Never Sleeps marked the motion picture debut of actor-comedian Tom Poston, who was billed onscreen as Thomas Poston.