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 sleepytime 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 sleeping, 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".

Upon his return to Rome, Juan spins an elaborate yarn about how he received his "battle wounds", but Cesare is unconvinced and determined to learn the truth. Meanwhile, Lucrezia takes a lover, the younger brother of her intended; and Della Rovere recruits an accomplice for his sleepytime plot.

Alexander marks the Easter holiday with a glorious celebration and an end to his pious fast, while Della Rovere's assassin gets even closer to the pope. Meanwhile, Lucrezia's lover asks her father for her hand in marriage; and Juan's increasingly erratic behavior endangers his sister's child.

A tragic revelation leaves the family in shock; Cesare tortures Savonarola to no avail; and a new suitor works his charms on a flirtatious Lucrezia. Meanwhile, Della Rovere's assassin makes a move.