Volpone, childless and rich, and his servant and parasite, Mosca, are playing a cunning and farcical game of deceit with three supposed friends who have each set their sights on becoming Volpone's sole heir. Volpone, although healthy, feigns deathly illness to urge the three to shower him with valuable gifts in hopes of gaining his favor, and soon his money.
Mosca assures each hopeful donor that each is the one whom Volpone has honored in an alleged will. First comes Voltore, whom Mosca promises is the sole heir. Next comes Corbaccio, whom Mosca advises to go home, disinherit his own son, and leave his fortune to Volpone. In return for this generous deed, Volpone, soon to die, would leave his fortune to Corbaccio, whose son would benefit eventually. Finally comes Corvino, whom Mosca convinces should have his wife sleep by Volpone's side, supposedly as a cure, but more likely as enough excitement to finally bring on the demise of the old man. Finally, Mosca tells Bonario, Corbaccio's son, that his father is about to disinherit him, and he promises to lead Bonario to a place where he can witness his father's betrayal.
The hilarity mounts even further with Lady Politick Would-Be, who is so talkative Volpone fears she will make him sick in actuality. To relieve his master's distress, Mosca tells the lady that her husband is riding off in a gondola with a young girl, and jealous Lady Would-Be hurries off in pursuit.
Volpone retires to a private closet, while Mosca leads Bonario behind a curtain so the young man can spy on his father. At that moment, eager to win favor with Volpone, Corvino arrives with Celia, and Mosca has to send Bonario off to another room so he can deal privately with Corvino.
Corvino has promised his wife that Volpone is too old to harm her and insists that she lie with the old fox. Yet, when Corvino leaves, Volpone leaps from his couch and attempts to force himself upon her. Bonario reappears just in time to save her, and Mosca and Volpone, in terror of exposure, bewail their ruined plot.
They are interrupted by Corbaccio, whom Mosca assures of Volpone's forthcoming death. Voltore interrupts this, and Mosca assures him that he is attempting to get possession of Corbaccio's money so that Voltore will inherit more from Volpone. Mosca further explains that Bonario had mistaken Celia's visit and had burst upon Volpone and threatened to kill him. Taken in by Mosca's lies, Voltore, a lawyer, promises to keep Bonario from accusing Volpone of rape and Corvino of villainy; he orders the young man arrested.
In court the comedy twists tighter when Mosca proceeds with this case by having Corvino and Corbaccio testify against Celia and Bonario, while he whispers to the avaricious old gentlemen that they are helping "justice." To add to the testimony, Mosca presents Lady Would-Be, who tells the court she has seen Celia beguiling Sir Politick in a gondola. Mosca, of course, promises Lady Would-Be that her name would stand first on Volpone's list of heirs.
When the trial is over, Volpone sends his servants to announce that he is dead and that Mosca is his heir. Mosca then greets all the spurned men as he sits in Volpone's house, supposedly taking inventory. Volpone, in the meantime, disguises himself as a commodore, in hopes of escaping from Venice with his loot.
However, having lost his hopes for the inheritance, Voltore begins to unwittingly unravel the plot. He withdraws his false testimony, and the court orders Mosca to appear. Suspecting that Mosca plans to keep the fortune for himself, Volpone also goes to the court, where he exposes to the court the foolish behavior of Corbaccio, Corvino, and Voltore, as well as the innocence of Celia and Bonario. The court sentences each conspirator, including Volpone and Mosca, according to the severity of his crime. Bonario is restored to his father's inheritance, and Celia is allowed to return to her father because Corvino has attempted to barter her honor for wealth.