Count Lodovico, a once noble man, has been banished from Rome for murder and corruption, yet his supporters vow to help repeal the banishment. Meanwhile, Duke Bracciano has been conducting an affair with Vittoria Corombona, behind the back of his wife Isabella. Flamineo, Vittoria's sister and aid to Bracciano helps to distract Vittoria's husband, Camillo, and enables the lovers to meet. Vittoria and Flamineo's brother Marcello and their mother Cornelia become increasingly horrified by the shame of the affair. The news arrives that Bracciano's wife, Isabella, is about to arrive in Rome and a plot is hatched to kill both her and Vittoria's husband Camillo.
Isabella arrives at court with her brother Francisco, the Duke of Florence, who, together with Cardinal Monticelso, is outraged at the news of Bracciano's affair. They are swift to confront Bracciano over his infidelity. Bracciano is confronted by Isabella , who, understanding that all is lost and still in love with her husband, selflessly takes the blame for the divorce and leaves. Flamineo and Bracciano hire a corrupt doctor in order to carry out the murder of Isabella, who is brutally disposed of. Elsewhere, during a drunken night out, Flamineo oversees the breaking of Camillo's neck.
Vittoria is arrested under suspicion of murdering her husband, and a trial takes place in which she is both interrogated and judged by cardinal Monticelso. She defends herself vehemently, but is sent to a house for penitent whores by the cardinal. Francisco learns of the death of his sister Isabella, and later sees a vision of her ghost, leading him to vow to avenge Isabella's death. Bracciano and Vittoria plot their escape to Padua where they will be married. Lodovico returns to Rome, reveals his secret love for Isabella to Franscisco and vows to avenge her death.
Monticelso is announced as the new pope, and the news arrives that Vittoria and Bracciano have fled to Padua. Monticelso excommunicates them and Francisco's plan to hire Ludovico takes shape.
Bracciano and Vittoria celebrate their wedding in Padua and Francisco joins them, disguised as a warrior named Mulinassar. Lodovico accompanies him, in the disguise of a monk. Lodovico succeeds in poisoning Brachaino during his wedding celebrations. Lodovico, still conealed as a monk, is left to preside over Bracciano's death bed, where he brutally strangles him. Flamineo concludes that her only way out is to kill her sister Vittoria, but despite all her efforts to do so, both Flamenio, Vittoria and their maid Zanche are killed by Lodovico, who is then finally sentenced to prison.