[The Revenger's Tragedy] opens in an Italian court. Vindice laments the death of his beloved Gloriana some years back. She died at the hands of the Duke, who poisoned her because she would not give in to his lustful advances. Hippolito, Vindice's brother, enters and tells Vindice that he may have found a way for Vindice to exact his revenge on the Duke. Lussurioso, the Duke's son, has asked Hippolito, one of his counselors, to find him a pander (a person who specializes in procuring women). The brothers agree that Vindice should disguise himself as a pander in order to get closer to the Duke.
Meanwhile, Junior, the Duke's stepson, has been arrested for the rape of Antonio's wife, a noblewoman. The Duchess tearfully pleads with her husband to vindicate the young man, but the Duke only goes so far as to ask the judges for a stay of execution. The Duchess is secretly infuriated. Her other two sons, Ambitioso and Supervacuo, vow to help their brother. The Duke's bastard son, Spurio, is also present at the trial. He feels resentment towards his father because of his illegitimacy, so the Duchess decides to seduce Spurio in order to wrangle his support in her vengeful plan against the Duke. Spurio does not love the Duchess, but decides to sleep with her to make his father angry.
Vindice disguises himself as the pander and meets with Lussurioso. The Duke's son is pleased with their introductory conversation and gives Vindice his first task: Lussurioso desires a young woman named Castiza who happens to be Vindice's own sister. Lussurioso instructs Vindice to first approach the chaste young woman, and if that does not work, he should try to bribe her mother instead. Vindice agrees, even though he is seething inwardly. After Lussurioso is gone, Vindice vows revenge on him, too, but decides to use this opportunity to test his mother and sister's moral judgement.
Antonio, meanwhile, sadly informs Vindice and another nobleman, Piero, that his wife has committed suicide due to the shame of being raped. Hippolito unites the noblemen in an oath to avenge Antonio's loss.
Vindice visits his sister in disguise and tries to convince her to give herself to Lussurioso. Castiza steadfastly resists him, determined to preserve her purity. However, Gratiana (Vindice, Hippolito, and Castiza's mother) falls prey to the fake pander's honeyed tongue and agrees to exchange her daughter for gold. While Vindice is horrified at his mother's quick downfall, he does not reveal his identity.
Vindice informs Lussurioso of his success, all the while planning his own revenge against the Duke and his son. Hippolito comes to Lussurioso with a new piece of gossip: the bastard Spurio and his stepmother, the Duchess, are planning to dishonor the Duke by fornicating. Lussurioso is infuriated and plans his own revenge. He bursts into the Duchess's bedroom in an attempt to witness her betrayal, but instead, he finds the Duke there. The Duke sends Lussurioso to prison for treason.
The Duke's stepsons pretend to be upset that Lussurioso is going to be executed, and the Duke sends them with an execution order for some days hence. After the brothers leave, the Duke gives a countermanding order to his officials, instructing them to release Lussurioso immediately.
Ambitioso and Supervacuo despise their stepfather (the Duke) and their stepbrother (Lussurioso) and plot to bring about their joint demise. They exult in Lussurioso's putative execution and visit their brother Junior to assure him that they have a plan to get him out. They hand the guards the order for the Duke's son to be executed, but the guards misinterpret it because there is no distinct name. After the brothers leave, the guards execute Junior. Lussurioso is freed.
Vindice and Hippolito confer. Vindice reveals that the Duke has also asked "the pander" to bring him a young woman, leading Vindice to hatch a plan. He has dressed up Gloriana's skull in a woman's clothes smeared poison on her lips so that when the Duke tries to kiss her, he will die.
The plan proceeds perfectly; the Duke kisses the skull, thinking it to be a real woman, and falls down as the poison takes hold. The brothers see the second part of their plan work out as well, for they have brought the Duke to the place where Spurio and the Duchess are carrying on their affair. The Duke dies, aghast and humiliated.
Lussurioso meets his stepbrothers, who are astonished at Lussurioso's escape from prison. They learn their own brother was executed, and continue to vow revenge against their stepbrother. Meanwhile, Ambitioso is becoming wary of Supervacuo because it seems like Supervacuo is also plotting to take power and leave his brother behind.
Lussurioso and Hippolito converse. Lussurioso tells Hippolito that he is unhappy with the pander and wants to find a new person to take care of his needs. Hippolito tells Lussurioso that he has a brother who will surely fit the bill. Vindice (this time out of disguise) meets with Lussurioso and Lussurioso, ironically, asks him to kill the pander (who is, of course, Vindice himself). Amused, Vindice agrees. He and Hippolito come up with yet another plan – they will dress up the Duke's body in Vindice's pander disguise and when Lussurioso sees the body, he will assume that the pander killed the Duke and then fled.
Ambitioso and Supervacuo learn that their mother is sleeping with Spurio and plan to kill the bastard. Meanwhile, Vindice confronts his mother, tells her about his disguise, and reveals that he is aware of her willingness to become a bawd for her daughter. Gratiana becomes hysterical and begs forgiveness, apologizing for her grievous betrayal. Vindice feels assured that she is legitimately sorry.
Vindice and Hippolito bring Lussurioso to the Duke's body, which is dressed in the pander's clothing. Lussurioso concludes exactly what the brothers hoped he would conclude - that the pander murdered the Duke and then fled. The Duchess and Spurio enter and see the Duke's body; both are secretly pleased to learn of his death. The other nobles tell Lussurioso that he will now be the leader of the kingdom; he pretends to be humble but is extremely glad to seize power. He decides to exile his stepmother. Everyone prepares for the revels that will follow Lussurioso's coronation. Vindice and Hippolito recruit two other men for their final plot. They will dress up in masks and then carry out their ultimate revenge at the revels.
As the revels begin, Lussurioso points out a blazing star in the sky, which is supposedly an ominous omen. The Revengers, wearing masks, come out and perform their dance. They then kill an unassuming Lussurioso and the three other men at his high table. Moments later, Ambitioso and Supervacuo enter, also wearing masks, and are surprised to see the carnage. Ambitioso slays his brother. Spurio slays Ambitioso. Another lord slays Spurio.
Vindice and Hippolito (whose involvement in the bloodbath remains concealed) call for the lord who killed Spurio to be seized. Vindice kneels down and gleefully reveals his true identity to the dying Lussurioso. Antonio and his followers are present; Antonio will be the new lord of the realm. Vindice cannot help himself and confesses to his complicity in all the deaths. Antonio is shocked and orders his guards to arrest Vindice and Hippolito. Antonio hopes that the brothers' deaths will purify the realm once and for all.