Vindice, the play’s protagonist, appears on stage holding skull of his deceased fiancée, Gloriana, who was killed nearly ten years ago by the Duke as punishment for refusing his advances. As the Duke and his entourage pass by, Vindice vows from the shadows to take his revenge.
Vindice meets with his brother, Hippolito, who is committed to helping Vindice impose his vengeful justice. Hippolito informs Vindice that Lussurioso, the Duke’s lusty son, asked Hippolito to procure a “pander” (a contemporary word for pimp) to help win the affections of an especially chaste virgin. Sensing an opportunity, Vindice disguises himself as “Piato” the pander and takes on Lussurioso’s mission—but to his horror the virgin in question is Castiza, his and Hippolito’s own sister.
Meanwhile, Junior Brother, the Duchess’s son (but not the Duke’s), is tried for the rape of the nobleman Antonio’s virtuous wife. The Duke refuses to pardon Junior Brother, leading the Duchess to plot revenge on her husband by having an affair with his bastard son, Spurio. Spurio agrees to the Duchess’ scheme, but more out of resentment towards his father for his illegitimacy than any true feelings towards her. Ambitioso and Supervacuo, the Duchess’s other two sons, vow to help their Junior Brother escape imprisonment; they hold their own ambitions to attain power too. Tragically, Antonio’s wife commits suicide because of her shame at being raped.
Vindice, disguised as Piato the pander, visits Castiza and tries to use his powers of persuasion to make her give up her virginal purity for Lussurioso. All he receives in return is a smack on the face, which he is privately grateful for, impressed by his sister’s commitment to her honor. But because he is playing the role of Piato, he turns his attentions to his and Castiza’s mother, Gratiana. With a silver tongue and a bribe, Vindice implores her to change Castiza’s mind; much to his horror, Gratiana agrees.
Vindice informs Lussurioso of the relative success of his visit, while privately doubling down on his commitment to kill both the Duke and the Duke’s son. Hippolito tells Vindice a rumor he has heard—that the Duchess is “cuckolding” the Duke by having an affair with Spurio. Vindice passes on this information to Lussurioso in an attempt to distract him from visiting Castiza; Lussurioso bursts into the Duchess’ chambers, but finds her with the Duke, not Spurio. Thinking his own son is attempting an act of treason, the Duke has Lussurioso imprisoned.
Supervacuo and Ambitioso pretend to plead with the Duke to be lenient with Lussurioso, while secretly aiming to speed up his execution. The Duke, sensing their ambitions, sends them to deliver a death warrant to the prison—which is mistakenly understood by the guards to be meant for Junior Brother. Meanwhile, the Duke has Lussurioso swiftly released.
The Duke, hearing of the pander’s skills, asks Piato (Vindice) to find him a virgin too. Vindice and Hippolito hatch a cunning and macabre plan: to dress up Gloriana’s skull as a living woman, place poison in her mouth, and then trick the Duke into kissing her. Their scheme works perfectly; as further vengeance, they orchestrate the Duke’s dying moments to be spent witnessing the illicit behavior of the Duchess and Spurio. Vindice makes sure to point out his true identity—and the skull’s—before the Duke passes away.
Soon after, Lussurioso comes to Hippolito to ask to meet his brother, Vindice. Upon their meeting, Lussurioso asks Vindice to assassinate Piato the pander, much to Vindice and Hippolito’s hidden amusement. Vindice and Hippolito come up with another ingenious idea: to dress the Duke up in the Piato disguise and pretend to kill him. After Lussurioso realizes it’s not the Duke, they reason, he will assume Piato himself killed the Duke and swapped their clothes in order to aid his getaway. Before bringing this plan to fruition, Hippolito and Vindice (now undisguised) visit Gratiana and force her to confess her immorality; satisfied with her repenting distress, they put their daggers away and praise her for changing her ways.
Vindice and Hippolito then bring Lussurioso to the Duke’s body, which is dressed in Piato’s clothes. Their plan works perfectly, with the Duke’s son concluding exactly what they had hoped. Lussurioso realizes that he is now at the top of the court hierarchy and makes plans for festivities to mark his ascension to the Dukedom, while pretending to grieve for his father. Vindice and Hippolito work out the final stage of their revenge: to dress up in costume and masks as part of the celebratory “masque”—a performance to be put on for Lussurioso—and kill him when his guard is down.
With Lussurioso crowned, the “revels” begin with a feast. Lussurioso notices a blazing star in the sky, usually a harbinger of terrible events—but reasons it away as he has already been made Duke. Vindice, Hippolito, and two accomplices burst in and fatally stab Lussurioso and his three noblemen. Almost immediately after, Spurio, Supervacuo, and Ambitioso arrive with the same murderous intentions. Seeing Lussurioso already dead, they turn on each other, and all three are quickly killed in the ensuing fight. Vindice kneels down to Lussurioso, who is drawing his last breaths, and gleefully reveals his true identity.
Hearing the commotion, Antonio comes in with guards and is shocked to behold the bloodbath in front of him. It’s quickly apparent that he is now the natural successor to the Dukedom. Antonio wonders what happened, and Vindice can’t help but reveal his role in the bloody events. Much to Vindice’s surprise, Antonio has him and Hippolito immediately sentenced to death, worried that they might plot against him too. Vindice accepts his fate, pleased to have brought about his revenge. As the brothers are led away, Antonio hopes that their deaths will bring an end to all the treason and tragedy.
