Pope Alexander fights for his life; the cardinals fight for control of the papacy; Cesare and Micheletto track the assassin; Della Rovere prepares to make his move.

Pope Alexander tasks Cardinal Sforza with initiating an inquisition among the Cardinals who were politicking against him. With the evidence he needs, Alexander dismisses and banishes all the Cardinals he does not trust. Meanwhile, Catherina Sforza orders Rufio to seek support from the mercenary warlords of the Romagna families. Lucrezia is annoyed with her in-laws to be and her situation is complicated further as she realizes her feelings for Cesare are becoming something more than sisterly.

As the purged Cardinals are dismissed and stripped of their titles and wealth, one of them angrily sets the Vatican treasury ablaze. Incensed by the new King Ferdinand’s arrogant refusal to accept Giovanni as Lucrezia’s child, Cesare travels to Naples to fix the problem. After Lucrezia and Alfonso’s wedding, Alfonso realizes that the political sands are shifting - and not in his favor. Upset, he abandons Lucrezia alone on their wedding night, driving her into the arms of someone else.

Newly appointed Cardinal Farnese (Cyron Melville) – promoted at the request of his sister Giulia (Lotte Verbeek) – is placed in the Treasury and quickly discovers Versucci’s theft. Micheletto (Sean Harris) is sent to find the wayward Cardinal. Meanwhile, upon hearing of Venice’s request for help against Turkish pirates, Alexander (Jeremy Irons), seeing this as an opportunity to replenish the coffers, dramatically calls for a Crusade. Concerned about the loyalty of his new Cardinals, Giulia arranges an orgy for them – the “banquet of chestnuts” – but it is a trap and details of the Cardinals’ sexual activities are recorded to extort their future loyalty. Elsewhere, King Ferdinand (Matias Varela) learns that Lucrezia (Holliday Grainger) and Alfonso’s (Sebastian De Souza) marriage has not been consummated and demands a public display of their love-making. Lucrezia is humiliated, but the experience seems to increase the incestuous attraction between her and her brother.

Cesare’s (Francois Arnaud) diplomatic mission to France is a success: guided through the complexities of the French court by his old advisor Machiavelli (Julian Bleach), Cesare makes an ally of Archbishop d’Amboise, a noble wife – Charlotte d’Albert – as well as a pledge of a military alliance against Milan and the Borgias’ enemies. Back in Rome, the seductive and dangerously insane Bianca (Melia Kreiling) takes her own life, prompting Alexander and Cardinal Sforza (Peter Sullivan) to conspire to repay Gonzaga’s cruel plot. Lucrezia travels to Naples accompanied by her husband, with Micheletto offering protection. King Ferdinand (Matias Varela) remains steadfast in his determination that little Giovanni will not be recognised at court. Upon learning this, Lucrezia plots against him with a recipe of poisonous mushrooms, but Micheletto will handle the matter on his own.

When Cesare lands in northern Italy with a French army, Alexander is furious at what he sees as a challenge to his authority, but reluctantly accedes to Cesare’s plan to destroy the Sforza dynasty, starting with Ludovico, Duke of Milan. Catherina (Gina McKee), meanwhile, has come up with a plot of her own: biological warfare. With the help of Rufio (Thure Lindhardt) she sends a plague-infected cloth, wrapped around a false message of peace, to Alexander. Cesare orders it destroyed unopened, but ambitious new Cardinal Constanzo disobeys and keeps the message for his own purposes, and soon, his household is in the grip of the plague. Concerned about the lack of funds for his Crusade, Alexander imposes punitive taxes on the newly arrived Jewish community. However one clever member of the community, Mattai (Brendan Cowell) claims to be able to procure a holy relic, the long lost Spear of Longinus. Cardinals Farnese and Petrucci vie to provide the Pope with the “real” relic, but Mattai gains the Pope’s respect and an unlikely alliance is born.

Cesare burns Constanzo’s palace – and the Cardinal with it – in order to contain the plague, while Micheletto is love struck with the beautiful young Pascal. Lucrezia, aware that the political wind has changed towards France and away from Naples, seeks a Neapolitan power base for herself and her family. There are two candidates to replace Ferdinand as King: arrogant and hostile Prince Raphael and kind and friendly Prince Frederigo. When Frederigo is apparently poisoned and almost dies, Lucrezia finds “evidence” of Raphael’s guilt and blackmails Raphael into giving up his claim. Her ally, Frederigo, is crowned King. But has she made the right choice?

Pilgrims are flooding to Rome for the Jubilee year celebrations, and the Spear of Longinus is the centerpiece of the show. However Catherina Sforza has a plan to frustrate Alexander’s lucrative festival. Across the sea in Kefalonia, the Turkish fleet is destroyed by Mattai’s (Brendan Cowell) Jewish contacts – Alexander shows his gratitude with a Bull exempting the community from taxes. Meanwhile, Lucrezia senses a change in newly crowned Frederigo, and realizes that she is under constant watch from the royal guard. The Borgias have walked into a trap: Lucrezia learns that Frederigo faked his near death to get Raphael out of the way, while at the same time in Rome, Cesare and Micheletto discover that the latter’s lover Pascal is a spy working for Rufio (Thure Lindhardt), reporting to a conspiracy of Catherina Sforza and King Frederigo of Naples. Lucrezia is not an honored princess in Naples, she is a hostage against any military moves against the Sforza family.

Devastated by his betrayal by Pascal, Micheletto kills his lover and subsequently disappears. Devastated by the loss of his loyal lieutenant, Cesare races to Naples to rescue Lucrezia, but she has already escaped her captors – with the aid of a sleeping potion. Brother and sister are reunited on the road back to Rome, and are so overjoyed to see one another that Alfonso (Sebastian De Souza) begins to suspect that their relationship seems more than that of ordinary siblings. Back in Rome, Alfonso becomes sullen and almost abusive, drinking heavily. Alexander, meanwhile, has come up with another plan with his friend Mattai (Brendan Cowell): they scheme to corner the market in Italian sulphur, thus denying anyone else the ability to manufacture gunpowder. Still, Alexander does not trust Cesare, who quickly uncovers his father’s plot, but it is Mattai who persuades father and son to reconcile.

Alexander and Cesare are reconciled at last, and the Pope reveals that the Papal Armies have been strengthened and re-equipped with the money saved from the Crusade and the proceeds of the Jubilee. Now, the Borgias are ready to move against their enemies the Sforzas and are ready to take their first step towards their ultimate goal: to carve out a hereditary kingdom across the heart of Italy. Cesare marches his fearsome army to lay siege to Catherina Sforza’s castle at Forli. Catherina is determined to resist despite the artillery bombardment and the danger of starvation in the bitter winter. Micheletto (Sean Harris) reappears from the shadows – his broken heart will not yet let him return to Cesare’s service, but he does advise Cesare of weak spots in Forli’s defences. Back in Rome, Cesare finds that Alfonso (Sebastian De Souza) has become even more aggressive and Cesare plans to murder him. But circumstances become deadly when a scuffle breaks out between Cesare and a drunk Alfonso. The doctor reports that Alfonso will certainly die, slowly and painfully over several days. Devastated, Lucrezia turns to her potions to end his life painlessly with Cesare vowing that now she will be his for good.