Neil Jordan had tried for over a decade to direct a film about the Borgia reign, with stars like Colin Farrell and Scarlett Johansson attached at different points before the project never came to fruition as a movie.

In 2010, Steven Spielberg, head of DreamWorks Pictures, suggested turning the film project into a cable drama, and Jordan pitched the idea to Showtime, which was looking to fill the gap left by the ending of The Tudors.

Neil Jordan envisioned an ideal run of four seasons to cover the span of Rodrigo Borgia's papacy (1492–1503), but the series was cancelled after three seasons, a season short of his planned arc.

Jeremy Irons initially had doubts about playing Rodrigo Borgia, since the historical figure was described as an obese, dark-complexioned Spaniard, but Jordan encouraged him to focus on the character's obsession with power rather than physical accuracy.

The series was an international co-production filmed mainly in Hungary, with much of the shooting taking place at Korda Studios in Etyek, just west of Budapest, while being produced in Canada.

After the cancellation in June 2013, plans for a two-hour wrap-up TV movie finale were scrapped due to cost; following a fan campaign to save the show, Showtime announced the unproduced finale script would instead be released as an ebook.

The show's first season received a mixed reception in the UK, with critics like Sarah Dempster of The Guardian mocking its dialogue and visual style, while the second season was met with markedly more positive reviews, jumping to a Metacritic score of 81/100 from 66/100.

The Borgias received 16 Emmy nominations over its run and won three, twice for Outstanding Costumes for a Series (2011 and 2013) and once for Outstanding Original Main Title Theme Music (2011); Jeremy Irons was also nominated for a Golden Globe in 2012.