In An Audience with Peter Ustinov (1988), Ustinov recalled that he had been attached to the role of Nero for over a year before filming began. During this time he received a memo from the producers, informing him that they still wanted him for the part, but were concerned that he was too young. Ustinov replied that Nero died when he was 31; if they waited much longer, he would be too old for the part. He then received a reply, which he said he had kept and treasured. The reply stated: "Historical research has proved you correct."
One immediate problem encountered with the lions was that when they were released from their cages, they found the arena so hot, they'd immediately retreat back into their cages to cool down. Director Mervyn LeRoy overcame this problem by having several costumes stuffed with raw meat and strewn around the ground. This made them appear to audiences to be "people", and the raw meat attracted the lions, who "attacked" and devoured them.
Nero remarks on the idea of creating an experience in order to gain inspiration, and complains that for his "conflagration", he has not yet seen a burning city. Petronius replies; "A burning city? That would be carrying art for art's sake too far". "Art for Art's Sake" is the English translation of "Ars Gratia Artis", which is the motto of MGM, the studio that produced and released this film.
Filmed at the new Cincecitta Studio in Rome, a long-delayed production complex originally conceived by Benito Mussolini and Hal Roach under their proposed R.A.M. ("Roach and Mussolini") Corporation, which was ultimately aborted. This fascist business alliance horrified 1930s' studio moguls and ultimately led to Roach defecting from his MGM distribution deal to United Artists in 1937. This new studio complex offered massive sets and cheap Italian labor. It would be later utilized by many producers, including Federico Fellini.
John Huston was originally supposed to direct, but walked out following arguments about the script. He was replaced by Mervyn LeRoy. Huston would have reportedly used father Walter Huston in the role of St. Peter.
True to his reputation as a voluptuary, the real Petronius took a week to kill himself by allowing his wounds to bleed and binding them up again. Reportedly he entertained friends, ate, drank and slept during the week-long ordeal.
The film does not cover the death of Paul, although he is acknowledged to have been martyred in 67 A.D. It is unclear if he died the same day as Peter and there is disagreement whether he was beheaded or crucified. Unlike Peter, Paul was a Roman citizen and by law no citizen could be crucified.
The film represented a hollow victory for MGM studio chief Louis B. Mayer, since it turned out to be his final big-budget production. Produced for $7 million, it was MGM's largest grosser since Gone with the Wind (1939), but Mayer was forced out of his job prior to its release.
Robert Taylor's chest reportedly had to be shaved for his part because the studio feared its hairiness might be too "sexy" for a biblical film. However, both of Taylor's "beefcake" scenes in the movie still show chest hair.
The property "Quo Vadis" was being developed by producer Arthur Hornblow in the 1940s. A September 7, 1943, news column by Sheilah Graham reported that Hornblow was considering Laraine Day for a key role.