The show was originally going to have four seasons, but when Neil Jordan thought about doing the fourth season, he didn't have the energy or even story to do ten episodes. Instead of that, he proposed Showtime to wrap up everything with a two-hour television movie. He even wrote the screenplay, but the network refused, arguing it was too expensive, and the season three ending worked as a series finale. Jordan eventually published the screenplay as an e-book called "The Borgia Apocalypse".
The Borgias were also the subject of Mario Puzo's novel The Family, and were the inspiration for the Corleone family in his best known novel, The Godfather. Rodrigo became Vito, Cesare became Michael, Juan became Santino ("Sonny"), Jofre became Fredo, and Lucrezia became Connie.
Originally, season one was going to have 10 episodes, but according to Neil Jordan, they ran out of money and had to adapt to nine.
The series has several ties to Showtime's previous period series epic, The Tudors. Both were produced by (amongst others) Sheila Hockin, and cast by Frank and Nuala Moiselle. Additionally, a shot of Natalie Dormer as Anne Boleyn is visible in both series' opening themes.
During the filming of season two, Francois Arnaud tripped and fell on-set, breaking his left elbow. He was in a cast for several weeks. In much of the last half of the season Cesare's arm is bent, hidden underneath his costumes, or resting on something. In the last two episodes of the season, if you look closely, you can see that the left arm is slightly thicker than the right underneath his sleeve.