Volpone takes place in seventeenth-century Venice, over the course of one day. The play opens at the house of Volpone, a Venetian nobleman. He and his "parasite" Mosca—part slave, part servant, part lackey—enter the shrine where Volpone keeps his gold. Volpone has amassed his fortune, we learn, through dishonest means: he is a con artist. And we also learn that he likes to use his money extravagantly.
Soon, we see Volpone's latest con in action. For the last three years, he has been attracting the interest of three legacy hunters: Voltore, a lawyer; Corbaccio, an old gentleman; and Corvino, a merchant—individuals interested in inheriting his estate after he dies. Volpone is known to be rich, and he is also known to be childless, have no natural heirs. Furthermore, he is believed to very ill, so each of the legacy hunters lavishes gifts on him, in the hope that Volpone, out of gratitude, will make him his heir. The legacy hunters do not know that Volpone is actually in excellent health and merely faking illness for the purpose of collecting all those impressive "get-well" gifts.
In the first act, each legacy hunter arrives to present a gift to Volpone, except for Corbaccio, who offers only a worthless (and probably poisoned) vial of medicine. But Corbaccio agrees to return later in the day to make Volpone his heir, so that Volpone will return the favor. This act is a boon to Volpone, since Corbaccio, in all likelihood, will die long before Volpone does. After each hunter leaves, Volpone and Mosca laugh at each's gullibility. After Corvino's departure Lady Politic Would-be, the wife of an English knight living in Venice, arrives at the house but is told to come back three hours later. And Volpone decides that he will try to get a close look at Corvino's wife, Celia, who Mosca describes as one of the most beautiful women in all of Italy. She is kept under lock and key by her husband, who has ten guards on her at all times, but Volpone vows to use disguise to get around these barriers.
The second act portrays a time just a short while later that day, and we meet Sir Politic Would-be, Lady Politic's husband, who is conversing with Peregrine, an young English traveler who has just landed in Venice. Sir Politic takes a liking to the young boy and vows to teach him a thing or two about Venice and Venetians; Peregrine, too, enjoys the company of Sir Politic, but only because he is hilariously gullible and vain. The two are walking in the public square in front of Corvino's house and are interrupted by the arrival of "Scoto Mantua," actually Volpone in diguise as an Italian mountebank, or medicine-show man. Scoto engages in a long and colorful speech, hawking his new "oil", which is touted as a cure-all for disease and suffering. At the end of the speech, he asks the crows to toss him their handkerchiefs, and Celia complies. Corvino arrives, just as she does this, and flies into a jealous rage, scattering the crows in the square. Volpone goes home and complains to Mosca that he is sick with lust for Celia, and Mosca vows to deliver her to Volpone. Meanwhile, Corvino berates his wife for tossing her handkerchief, since he interprets it as a sign of her unfaithfulness, and he threatens to murder her and her family as a result. He decrees that, as punishment, she will now no longer be allowed to go to Church, she cannot stand near windows (as she did when watching Volpone), and, most bizarrely, she must do everything backwards from now on–she must even walk and speak backwards. Mosca then arrives, implying to Corvino that if he lets Celia sleep with Volpone (as a "restorative" for Volpone's failing health), then Volpone will choose him as his heir. Suddenly, Corvino's jealousy disappears, and he consents to the offer.
The third act begins with a soliloquy from Mosca, indicating that he is growing increasingly conscious of his power and his independence from Volpone. Mosca then runs into Bonario, Corbaccio's son, and informs the young man of his father's plans to disinherit him. He has Bonario come back to Volpone's house with him, in order to watch Corbaccio sign the documents (hoping that Bonario might kill Corbaccio then and there out of rage, thus allowing Volpone to gain his inheritance early). Meanwhile Lady Politic again arrives at Volpone's residence, indicating that it is now mid-morning, approaching noon. This time, Volpone lets her in, but he soon regrets it, for he is exasperated by her talkativeness. Mosca rescues Volpone by telling the Lady that Sir Politic has been seen in a gondola with a courtesan (a high-class prostitute). Volpone then prepares for his seduction of Celia, while Mosca hides Bonario in a corner of the bedroom, in anticipation of Corbaccio's arrival. But Celia and Corvino arrive first—Celia complains bitterly about being forced to be unfaithful, while Corvino tells her to be quiet and do her job. When Celia and Volpone are alone together, Volpone greatly surprises Celia by leaping out of bed. Celia had expected and old, infirm man, but what she gets instead is a lothario who attempts to seduce her with a passionate speech. Always the good Christian, Celia refuses Volpone's advances, at which point Volpone says that he will rape her. But Bonario, who has been witnessing the scene from his hiding place the entire time, rescues Celia. Bonario wounds Mosca on his way out. Corbaccio finally arrives, too late, as does Voltore. Mosca plots, with Voltore's assistance, how to get Volpone out of this mess.
A short while later, in the early afternoon, Peregrine and Sir Politic are still talking. Sir Politic gives the young traveler some advice on living in Venice and describes several schemes he has under consideration for making a great deal of money. They are soon interrupted by Lady Politic, who is convinced that Peregrine is the prostitute Mosca told her about—admittedly, in disguise. But Mosca arrives and tells Lady Politic that she is mistaken; the courtesan he referred to is now in front of the Senate (in other words, Celia). Lady Politic believes him and ends by giving Peregrine a seductive goodbye with a coy suggestion that they see each other again. Peregrine is incensed at her behavior and vows revenge on Sir Politic because of it. The scene switches to the Scrutineo, the Venetian Senate building, where Celia and Bonario have informed the judges of Venice about Volpone's deceit, Volpone's attempt to rape Celia, Corbaccio's disinheritance of his son, and Corvino's decision to prostitute his wife. But the defendants make a very good case for themselves, led by their lawyer, Voltore. Voltore portrays Bonario and Celia as lovers, Corvino as an innocent jilted husband, and Corbaccio as a wounded father nearly killed by his evil son. The judge are swayed when Lady Politic comes in and (set up perfectly by Mosca) identifies Celia as the seducer of her husband Sir Politic. Further, they are convinced when Volpone enters the courtroom, again acting ill. The judges order that Celia and Bonario be arrested and separated.
In the final act, Volpone returns home tired and worried that he is actually growing ill, for he is now feeling some of the symptoms he has been faking. To dispel his fears, he decides to engage in one final prank on the legacy hunters. He spreads a rumor that he has died and then tells Mosca to pretend that he has been made his master's heir. The plan goes off perfectly, and all three legacy hunters are fooled. Volpone then disguises himself as a Venetian guard, so that he can gloat in each legacy hunter's face over their humiliation, without being recognized. But Mosca lets the audience know that Volpone is dead in the eyes of the world and that Mosca will not let him "return to the world of the living" unless Volpone pays up, giving Mosca a share of his wealth.
Meanwhile, Peregrine is in disguise himself, playing his own prank on Sir Politic. Peregrine presents himself as a merchant to the knight and informs Politic that word has gotten out of his plan to sell Venice to the Turks. Politic, who once mentioned the idea in jest, is terrified. When three merchants who are in collusion with Peregrine knock on the door, Politic jumps into a tortoise-shell wine case to save himself. Peregrine informs the merchants when they enter that he is looking at a valuable tortoise. The merchants decide to jump on the tortoise and demand that it crawls along the floor. They remark loudly upon its leg-garters and fine hand-gloves, before turning it over to reveal Sir Politic. Peregrine and the merchants go off, laughing at their prank, and Sir Politic moans about how much he agrees with his wife's desire to leave Venice and go back to England.
Meanwhile, Volpone gloats in front of each legacy hunter, deriding them for having lost Volpone's inheritance to a parasite such as Mosca, and he successfully avoids recognition. But his plan backfires nonetheless. Voltore, driven to such a state of distraction by Volpone's teasing, decides to recant his testimony in front of the Senate, implicating both himself but more importantly Mosca as a criminal. Corvino accuses him of being a sore loser, upset that Mosca has inherited Volpone's estate upon his death, and the news of this death surprises the Senators greatly. Volpone nearly recovers from his blunder by telling Voltore, in the middle of the Senate proceeding, that "Volpone" is still alive. Mosca pretends to faint and claims to the Senate that he does not know where he is, how he got there, and that he must have been possessed by a demon during the last few minutes when he was speaking to them. He also informs the Senators that Volpone is not dead, contradicting Corvino. All seems good for Volpone until Mosca returns, and, instead of confirming Voltore's claim that Volpone is alive, Mosca denies it. Mosca, after all, has a will, written by Volpone and in his signaure, stating that he is Volpone's heir. now that Volpone is believed to be dead, Mosca legally owns Volpone's property, and Mosca tells Volpone that he is not going to give it back by telling the truth. Realizing that he has been betrayed, Volpone decides that rather than let Mosca inherit his wealth, he will turn them both in. Volpone takes off his disguise and finally reveals the truth about the events of the past day. Volpone ends up being sent to prison, while Mosca is consigned to a slave galley. Voltore is disbarred, Corbaccio is stripped of his property (which is given to his son Bonario), and Corvino is publicly humiliated, forced to wear donkey's ears while being rowed around the canals of Venice. At the end, there is a small note from the playwright to the audience, simply asking them to applaud if they enjoyed the play they just saw.