Extremely ruthless and ambitious cardinal Rodrigo Borgia uses bribery to take advantage of the death of the current Pope and rise to the Papacy.

Micheletto, Orsini's assassin is recruited by Cesare to defect into the service of Della Rovere who is trying to prove Rodrigo has taken on a mistress.

Sultan Cem of the Ottoman Empire arrives at Rome. Cesare declines his brothers request of using Michelotto. The Pope tries to decide who is to marry his daughter.

Cesare Borgia takes the beautiful Ursula Bornadeo as his mistress and vows to revenge himself on her husband who has insulted his mother.

In order to ensure a lasting alliance with Naples, the Pope betroths his 13 year old son to his bastard daughter while Della Rovere conspires in France.

Della Rovere convinces the French king to invade Milan and is aghast at the slaughter while Cesare discovers the abbey where Ursula has retreated after her husband's death.

Paolo helps Lucrezia and Guilia escape Sforza, but they are captured by advancing French forces as the Pope's cardinals flee Rome before King Charles' military juggernaut.

The Pope disarms King Charles by promising his support for his Neapolitan claims, and wishes to annul Lucrezia's marriage on grounds of her husband's impotency.