Pope Alexander VI takes a new lover and throws a grand, pagan fete for the citizens of Rome when a cache of ancient artifacts is discovered; the rivalry between brothers Cesare and Juan spills into the streets; Lucrezia tends to her newborn child; now a pastoral priest once again, Della Rovere narrowly escapes an assassination attempt

The stable boy who fathered Lucrezia's child travels to Rome to rendezvous with her but suffers an unfortunate fate at the hands of Juan; the Pope's lovers Giulia and Vittoria take him in disguise on a revelatory tour of Rome's indigent.

Alexander VI refuses to allow a Catholic burial for Paolo, despite his doubts about the stable boy’s suicide, causing Lucrezia to embark on a hunger strike that threatens the life of her infant son; the French army heads back to Rome, allied with Sforza; Della Rovere slips back into the city unnoticed to launch a plot against the Pope’s life.

Cesare recruits a band of mercenaries with the help of Micheletto to seek revenge on the retreating French troops for burning the nunnery where his beloved Ursula lived; the Pope forges more strategic alliances and enriches himself in the bargain; Lucrezia joins Giulia's quest to aid Rome's poor.

Cesare deals with the cunning Sforzas decisively; Alexander disguises himself and travels to Florence to hear the fiery preacher Savonarola, not realizing that Della Rovere is trying to recruit the rebellious holy man to his cause.

Alexander is convinced that a lightning strike on St. Peter's Basilica during mass was a sign of God's disapproval; Cesare tries to prove his worth as a military commander; the Pope pressures the reluctant Lucrezia to enter another political marriage.

Juan's triumphant return from Spain is marred by his unsuccessful siege of the Sforza castle; Lucrezia purposely scuttles a scheme to marry her off to a rich Genovese merchant; Savonarola's forces conduct the infamous "Bonfire of the Vanities."

Juan returns to Rome trying to spin his combat injury as proof of his valor, but Cesare exposes his brother's ignoble behavior; Lucrezia takes a lover in her intended husband's younger brother; Della Rovere has recruited an angel-faced young friar as his suicide assassin, and the young man advances their agenda with a bold move against the Pope's food taster.

It’s Easter, but Alexander continues to fast. A new taster is recruited, and Antonello gets the job – Della Rovere’s assassin is ready to strike. In Florence, Cesare challenges Savonarola to a trial by fire. Raffaello meanwhile, formally asks for Lucrezia’s hand but Alexander sends the brothers packing. Giulia persuades Alexander that his Papacy has been a good thing, so he ends his fast and orders a celebration for the baptism of Lucrezia’s baby. At the party, Antonello is ready to strike but is thwarted by Alexander’s switch from water back to wine. As the party continues, Juan is completely out of control, and threatens the life of Lucrezia’s child. A chilling Cesare at last comes to terms with what needs to be done.

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