An outbreak of plague in London forces a gentleman, Lovewit, to flee temporarily to the country, leaving his house under the sole charge of his butler, Jeremy. Jeremy uses the opportunity given to him to use the house as the headquarters for fraudulent acts. He transforms himself into "Captain Face," and enlists the aid of Subtle, a fellow conman, and Doll Common, a prostitute.
The play opens with a violent argument between Subtle and Face concerning the division of the riches which they have, and will continue to gather. Doll breaks the pair apart and reasons with them that they must work as a team if they are to succeed. Their first customer is Dapper, a lawyer's clerk who wishes Subtle to use his supposed necromantic skills to summon a "familiar" or spirit to help in his gambling ambitions. The tripartite suggest that Dapper may win favour with the "Queen of Fairy," but he must subject himself to humiliating rituals in order for her to help him. Their second gull is Drugger, a tobacconist, who is keen to establish a profitable business. After this, a wealthy nobleman, Sir Epicure Mammon, arrives, expressing the desire to gain himself the philosopher's stone, which he believes will bring him huge material and spiritual wealth. He is accompanied by Surly, a sceptic and debunker of the whole idea of alchemy. He is promised the philosopher's stone and promised that it will turn all base metal into gold. Surly however, suspects Subtle of being a thief. Mammon accidentally sees Doll and is told that she is a Lord's sister who is suffering from madness. Subtle contrives to become angry with Ananias, an Anabaptist, and demands that he should return with a more senior member of his sect (Tribulation). Drugger returns and is given false and ludicrous advice about setting up his shop; he also brings news that a rich young widow (Dame Pliant) and her brother (Kastril) have arrived in London. Both Subtle and Face in their greed and ambition seek out to win the widow.
The Anabaptists return and agree to pay for goods to be transmuted into gold. These are in fact Mammon's goods. Dapper returns and is promised that he shall meet with the Queen of Fairy soon. Drugger brings Kastril who, on being told that Subtle is a skilled match-maker, rushes to fetch his sister. Drugger is given to understand that the appropriate payment might secure his marriage to the widow. Dapper is blindfolded and subjected to 'fairy' humiliations; but on the reappearance of Mammon, he is gagged and hastily thrust into the privy. Mammon is introduced to Doll. He has been told that Doll is a nobleman's sister who has gone mad, but he is not put off, and pays her extravagant compliments. Kastril and his sister come again. Kastril is given a lesson in quarrelling, and the widow captivates both Face and Subtle. They quarrel over who is to have her.
Surly returns, disguised as a Spanish nobleman. Face and Subtle believe that the Spaniard speaks no English and they insult him. They also believe that he has come for a woman, but Doll is elsewhere in the building 'engaged' with Mammon, so Face has the inspiration of using Dame Pliant. She is reluctant to become a Spanish countess but is vigorously persuaded by her brother to go off with Surly. The tricksters need to get rid of Mammon. Doll contrives a fit and there is an 'explosion' from the 'laboratory'. In addition, the lady's furious brother is hunting for Mammon, who leaves. Surly reveals his true identity to Dame Pliant and hopes that she will look on him favourably as a consequence. Surly reveals his true identity to Face and Subtle, and denounces them. In quick succession Kastril, Drugger and Ananias return, and are set on Surly, who retreats. Drugger is told to go and find a Spanish costume if he is to have a chance of claiming the widow. Doll brings news that the master of the house has returned.
Lovewit's neighbours tell him that his house had many visitors during his absence. Face is now the plausible Jeremy again, and denies the accusation—-he has kept the house locked up because of the plague. Surly, Mammon, Kastril and the Anabaptists return. There is a cry from the privy; Dapper has chewed through his gag. Jeremy can no longer maintain his fiction. He promises Lovewit that if he pardons him, he will help him obtain himself a rich widow (i.e., Dame Pliant). Dapper meets the "Queen of Fairy" and departs happily. Drugger delivers the Spanish costume and is sent to find a parson. Face tells Subtle and Doll that he has confessed to Lovewit, and that officers are on the way; Subtle and Doll have to flee, empty handed.
The victims come back again. Lovewit has married the widow and claimed Mammon's goods; Surly and Mammon depart disconsolately. The Anabaptists and Drugger are summarily dismissed. Kastril accepts his sister's marriage to Lovewit. Lovewit pays tribute to the ingenuity of his servant, and Face asks for the audience's forgiveness.