The film opens in Rome in 1492 at a pivotal moment in history. The three Borgia brothers—Juan, César, and Jofré—travel to the Vatican for a conclave to elect a new Pope. There, they learn their father, Rodrigo, has been chosen as the new pontiff, taking the name .
The favorite son, endowed with military command despite his profound incompetence and arrogance. His toxic rivalry with Cesare serves as the primary catalyst for the family's internal fracturing.
Elated by his new, unchecked power, the new Pope embarks on a ruthless plan to expand the Vatican's territories and secure his family's legacy. He arranges strategic marriages for his children, coupling Lucrezia with Giovanni Sforza and forcing Jofré to wed Sancha of Aragon, all to forge alliances with rival families.