Egeon of Syracuse has been arrested in Ephesus. We discover he is searching for his lost sons (twins, both called Antipholus). The law says that any citizen of Syracuse found in Ephesus will be executed unless he can pay a hefty fine. Egeon cannot pay but tells the Duke his story about losing his wife and one of his sons at sea. The Duke takes pity and delays the execution until sunset in the hope someone will come forward with the money.

Antipholus of Syracuse arrives in Ephesus with his servant, Dromio (also one of twins, both called Dromio). Unknown to them, their twin brothers both live in Ephesus. Dromio of Ephesus mistakes Antipholus of Syracuse for his master and tells him he is late home for dinner. Antipholus denies having a wife.

Adriana, the wife of Antipholus of Ephesus, is upset with him. She and her sister Luciana mistake Antipholus of Syracuse for her husband and confront him about having an affair. Confused, Antipholus of Syracuse goes home with them. Dromio of Syracuse follows.

The real Antipholus of Ephesus arrives home. Dromio of Syracuse refuses to let him in. Antipholus of Ephesus threatens to break the door down. He has ordered a gold chain as a present for Adriana but decides she does not deserve it and he'll give it to his friend the Courtesan instead.

Luciana tells Antipholus of Syracuse to comfort his wife Adriana; confused, he instead declares his love to Luciana. Dromio of Syracuse is also confused: a servant is also claiming to be his wife. Both men decide Ephesus is full of witchcraft.

Angelo, a goldsmith, gives the gold chain to Antipholus of Syracuse, mistaking him for his brother. Later when Angelo sees Antipholus of Ephesus, he asks him for the payment for the chain; of course, because he hasn’t seen the chain, he won’t pay. Angelo has him arrested and Antipholus sends Dromio of Syracuse (mistaking him for his own servant) to Adriana for money to bail him out of prison.

Dromio of Syracuse is very confused but collects the money from Adriana. When he returns, he meets his own master, Antipholus of Syracuse, who is delighted that Dromio has found room on a ship for them to escape from Ephesus but is confused why Dromio is giving him gold from Adriana. When the Courtesan arrives and demands the gold chain she’d been promised, Antipholus and Dromio of Syracuse run off, convinced she is a witch.

Adriana thinks her husband is going mad and employs a conjuror to cure him. Antipholus and Dromio of Ephesus are taken away. A few minutes later, Antipholus and Dromio of Syracuse appear. Everyone thinks they are their twins who have escaped and are out for revenge. The two men run into a priory where Emilia gives them shelter.

The Duke enters with Egeon who is about to be executed. Antipholus and Dromio of Ephesus reappear, having escaped their captors. Egeon recognises his son and appeals to him for help. But this is not the son he raised and Antipholus of Ephesus does not recognise him.

Antipholus and Dromio of Syracuse emerge from the priory. Both sets of twins truly see each other for the first time and we discover Emilia is Egeon's long lost wife and mother of the Antipholus twins. The family is reunited and the Duke spares Egeon's life.