For his role as Hobie Doyle, Alden Ehrenreich learned horseback riding, rope tricks, twirling guns, and playing the guitar. He has stated twirling the spaghetti, mimicking the lasso, was the hardest part of his role.
Dolph Lundgren has an uncredited (initially much longer and almost entirely deleted) cameo as the submarine Captain. Lundgren said that he was very honored to play the part, having never expected to be asked for a movie directed by Joel and Ethan Coen.
The Coen Brothers considered casting one hundred-year-old character actor Norman Lloyd as Herbert Marcuse, but changed their mind due to a scene in which he would have to appear on a boat in rocking water.
The Coen brothers had been brainstorming the story for a decade but never actually wrote anything. George Clooney, as a practical joke, announced 'Hail, Caesar!' as his next film at a press conference. The Coens received so much publicity over Clooney's statement that they were effectively forced to make the film for real.
The fictional movie studio "Capitol Pictures" previously appeared in Barton Fink (1991), another Los Angeles period movie from the Coen Brothers. Eddie Mannix's secretary mentions that his meeting with the four religious leaders takes place in the "Wallace Beery Conference Room". In the previous movie, Barton Fink was a screenwriter who was writing a script for Capitol Pictures, for a wrestling movie starring real-life actor Wallace Beery.