Supporting cast
Ronan Vibert as Giovanni Sforza: The Lord of Pesaro, picked as the husband of Lucrezia by the pope in exchange for support from the Sforza clan. A cold and beastly man, he rapes Lucrezia repeatedly at the beginning of the marriage. He breaks his leg after falling off a horse thanks to a scheme by stable boy Paolo out of love for Lucrezia. The household staff all hate him and several of them side with Lucrezia and aid her in her affair with Paolo. He betrays the alliance with the Borgias by refusing to support them against the impending French invasion. He is later publicly humiliated by the Borgias, who convene the College of Cardinals to have his marriage to Lucrezia annulled on the grounds of impotence. When Sforza denies the charges, the Pope declares that he must prove it before the College and two prostitutes are brought in. Sforza, unable to bear the humiliation, declares that he is impotent and is sent from Rome in disgrace. Later, after making snide comments about Lucrezia to Cesare, who is on a visit to Forli to negotiate peace with his cousin, Caterina Sforza, Cesare attacks and kills him, igniting a war between the Borgias and Caterina.
Edward Akrout as Yves d'Alègre (c. 1450 – battle of Ravenna, 1512): an outstanding French captain who became known in the early Italian Wars (1494–1512).
Steven Berkoff as Girolamo Savonarola: An influential priest in Florence who is eventually killed for preaching against the corruption in the Church and the leadership of the Borgias.
Simon McBurney as Johannes Burchard: The Vatican Master of Ceremonies and a scholar with impeccable expertise on canon law. To keep his position (and life), Johannes remains deliberately ambiguous about his loyalties, at times assisting both Pope Alexander VI and his enemies in their scheming.
Augustus Prew as Alfonso II of Naples: The eldest son of King Ferdinand I of Naples. His father was old and senile, leaving himself as the effective ruler of Naples. In the series, he is eventually tortured to death by King Charles VIII, who blamed him for the plague that swept Naples, and his body is placed in his father's gruesome "Last Supper" as Judas Iscariot. However, the historical Alfonso fled to a Sicilian monastery, dying non-violently in 1495
Luke Pasqualino as Paolo: The young servant of Giovanni Sforza. He is outraged by his master's treatment of Lucrezia and sabotages Sforza's saddle, causing his master to suffer a serious injury. He and Lucrezia later have an affair, and he fathers a child with her. He helps her escape from the Sforza household, which cost him a violent whipping from his master. He travels to Rome to search for her, naively befriending a prostitute whom Juan Borgia employs to follow him. With the help of Cesare and Micheletto, he is reunited with Lucrezia and his child for one night. Shortly after he is murdered by Juan, who hangs him to make it look like a suicide. Lucrezia is heartbroken by his death and forces her father to give Paolo a Christian burial, while also having her revenge on Juan for Paolo's murder.
Derek Jacobi as Cardinal Orsino Orsini (fictional character): One of the cardinals who plotted against Pope Alexander, he is poisoned to death at the instruction of Cesare Borgia.
Ruta Gedmintas as Ursula Bonadeo/Sister Martha: A noblewoman who engaged in a passionate extramarital affair with Cesare. Upon discovering Cesare killed her husband she becomes a nun and was thereafter known as Sister Martha. She is killed when the Convent of Saint Cecilia is destroyed by Charles VIII, on his way back to France after retreating from Rome. Her death fills Cesare with vengeance, and he leads a band of mercenaries to raid and destroy the French army, ultimately destroying their entire war machine.
Elyes Gabel as Prince Cem (Djem or Jem): A rival to the Ottoman throne, who was banished by his half-brother, the Sultan. Pope Alexander accepted the Sultan's offer to host Cem in exchange for financial reward. The handsome and good-hearted young man easily wins over the Borgias, especially Lucrezia. It is heavily implied that Cem and Lucrezia fall in love, but do not consummate their relationship. Cem was eventually killed by the Borgias, who used the much more substantial reward offered by the Sultan for Cem's death, in order to pay for Lucrezia's dowry.
Montserrat Lombard as Maria, a maid in the Orsini Palace during Giulia Farnese's stay there who is willing to testify on her indiscretions with the Pope and pays the price for it.
Emmanuelle Chriqui as Sancha of Aragon: The illegitimate daughter of the King of Naples. When a marriage to the Borgias was proposed, Juan refused to marry her due to her illegitimacy. She was married instead to Joffre, but Juan became struck by her beauty and began an affair with her.
Vernon Dobtcheff as Cardinal Julius Verscucci (fictional character)
Bosco Hogan as Cardinal Piccolomini
David Bamber as Theo: The estranged husband of Vanozza Cattaneo who was forced aside and barred from her life by Rodrigo Borgia prior to becoming pope. He lives on a remote farm the pope bought him but visits Vannozza during Lucrezia's first wedding. Cesare is civil but Juan beats him, for which the Pope severely chastises him. He is rumored to have fathered one of the Borgia children, which Juan suspects is him.
Peter Sullivan as Ascanio Sforza: A powerful cardinal who becomes vice-chancellor in a deal with Rodrigo Borgia to elect Borgia as pope. Sforza becomes a trusted confidant and henchman to the Borgias carrying out many duties that maintain their power and wealth.
Julian Bleach as Niccolò Machiavelli: A senior official in the Republic of Florence and adviser to the Medici family, he carefully considered the offers of alliance by Cardinal della Rovere and Cesare Borgia. Della Rovere pushes for Florence to give free passage of the French army on their way to Rome. He was upset when the Medicis yield hopelessly to the demands of the King of France in the face of total destruction of Florence by the French armies. He later allies with Cesare, providing advice on the matter of Savonarola and the location of Medici gold transports for Cesare to steal.
Ivan Kaye as Ludovico Sforza: The brutish Duke of Milan, also known as "il Moro," who seized the throne and imprisoned his own nephew in the process. Despite an alliance of the Sforzas and the pope, he allowed the French army free passage through Milan on the way to Rome.
Michel Muller as Charles VIII: King of France and commander of one of the most feared armies in Europe, Charles is a modernizing military leader who, in contrast to his theatrical opponents, conducts warfare with ruthless efficiency. He claimed the throne of Naples, and was enticed by Cardinal della Rovere to pursue this objective in return for deposing Pope Alexander. Insecure about his height and looks, he was charmed by the clever and beautiful Lucrezia Borgia on his way to seizing Rome, and later talked into an alliance by the pope, who agreed to recognize him as King of Naples. After discovering that Naples has been devastated by plague, he has Prince Alfonso II killed, but ends up catching the plague himself.
Darwin Shaw as Augustino, a childhood friend of Micheletto. The two briefly resume a passionate and intense romance, but Augustino's betrothal to a baker's daughter deeply hurts Micheletto.
David Lowe as the French Ambassador to Rome.
Sebastian de Souza as Alfonso of Aragon, Duke of Bisceglie and Prince of Salerno: He arrived in Rome as suitor to Lucrezia, who chose to marry him as a second husband.
Thure Lindhardt as Rufio: A student of the art of death, he is Caterina Sforza's ruthless assassin. He is sent to Rome by his patron to bring about the Borgias' downfall, and he tries to enlist Cardinal Sforza's help in doing so. At the end of season 3 with the Sforzas defeated Rufio is hired by Cesare.
Matias Varela as King Ferdinand in Season 3. Alfonso's uncle that demands proof of his nephew's consummated marriage to Lucrezia and refuses to recognize her son at court due to his illegitimacy thus incurring the wrath of Lucrezia and Cesare. He is killed by Micheletto, who pushes him into a fanciful lake of lampreys.
Cyron Melville as Cardinal Farnese in Season 3. He is Giulia Farnese's brother that is made a cardinal through his sister's intervention with the Pope. He manages the papal finances.
Pilou Asbæk as Paolo Orsini in Season 3.
Katie McGuinness, as Beatrice, in two episodes: "Paolo" and "The Choice" in Season 2.
Patrick O'Kane as Francesco Gonzaga.
Ana Ularu as Charlotte d'Albret, Dame de Châlus and Duchess of Valentinois. She became Cesare's wife following a pact made with King Louis XII of France to gain military support against the Sforza family.
Jemima West as Vittoria, a young girl who disguises herself as a boy in order to be apprenticed as an artist.
Joseph M. Kelly as Ferrante of Naples.
Harry Taurasi as Piero de Medici.
Luke Allen-Gale as Fredirigo.
Abraham Belaga as Vitelezzo Vitelli.
Björn Hlynur Haraldsson as Gian Paolo Baglioni.
Keith Burke as Gian Galaezzo.
Michael Poole as Pope Innocent.
Joseph Macnab as Prospero Colonna.
Pinturicchio is mentioned as a painter of Giulia Farnese in season 1, episode 2.
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