The patriarch of the Borgia family has been appointed Pope Alexander VI. This creates controversy because his wicked son Cesare has been accused of vile acts including murder and rape in the past. His other son, Juan, believes that Cesare has been driven to madness by his insane love for their sister, Lucrezia. Anyone who expresses an interest in the lovely Lucrezia is soon found murdered. This even extends to Juan, who is killed by his own brother for voicing his suspicions about Cesare's incestous obsession. When Alexander learns of Juan's death, he orders Cesare's capture and execution. Panicking, Cesare kidnaps Lucrezia and holes up in his castle, vowing that if he can't have his sister, no one can...

In Germany, the studio executives at UFA were aware of the enormous financial success that Italian historical epics like Quo Vadis (1913) and Cabiria (1914) had. Such films not only reaped great gains domestically, they also were more likely to find success in foreign countries. Along with the historical pageants directed by Ernst Lubitsch (1920's Passion and 1921's One Arabian Night) Lucrezia Borgia was one of UFA's attempts to match those Italian epics for spectacle and sheer audacity. Conrad Veidt, who gives one of his great performances as the crazed Cesare Borgia, had garnered worldwide acclaim for The Cabinet of Caligari in 1920. One of the highest-paid actors in Germany, Veidt would leave his home country to escape Nazi oppression in 1933. Settling in America, he made unforgettable performances in The Man Who Laughs (1928), The Thief of Bagdad (1940) and Casablanca (1942) before his far too young death in 1943. In addition to being an actress, Anita Berber was a cabaret dancer who often performed in the nude, making her one of the most scandalized figures in Weimar Germany (her otherworldly form was immortalized in an Otto Dix painting.) She, too, died young at the age of 29. Paul Wegener starred in another classic of the German cinema, The Golem (1915). William Dieterle later became a director in America, making classics such as The Story of Louis Pasteur (1936), The Hunchback of Notre Dame (1939) and The Devil and the Daniel Webster (1941). Director Richard Oswald had previously explored the-then taboo subject of homosexuality in his groundbreaking Different from the Others (1919) and made one of the first horror anthologies with Eerie Tales (1919).