The play begins with the trial of Egeon of Syracuse, who has been detained in Ephesus by the Duke Solinus. Egeon explains that he is in Ephesus because he is searching for his two twin sons and their twin servants. Two decades earlier, Egeon had lost his wife, one of his sons, and his son's servant at sea. He raised his other son, who eventually set out (with his own servant) to find his twin brother. When that son did not return, Egeon himself traveled to Ephesus to find his family. Solinus takes pity on Egeon (who, as a Syracusian, is not allowed in Ephesus), and tells him he has until the end of the day to raise money for ransom, otherwise he will be executed.
In a marketplace, Egeon's son Antipholus and his servant Dromio don outfits to make them look more like locals than Syracusians. They are unaware that their twin brothers are already living in Ephesus, having been rescued by fishermen after the storm took them. Both the Syracusian and the Ephesian twins have identical names.
As the two sets of twins happen upon one another, a series of confusing events ensues: Antipholus of Syracuse is confronted by Dromio of Ephesus, who is frustrated that Antipholus has not come home to his wife, Adriana. This leads Antipholus of Syracuse to dine with Adriana (who in reality is his sister-in-law), and he falls in love with her sister, Luciana. Dromio of Syracuse stands guard during the dinner and denies Antipholus of Ephesus entrance into what is really his own house.
Meanwhile, Antipholus of Ephesus ordered a gold chain that is mistakenly delivered to Antipholus of Syracuse. When they cannot pay, Antipholus of Ephesus and Dromio of Ephesus are arrested. Adriana thinks her husband has gone mad and hires a schoolmaster to exercise him and his servant (Antipholus and Dromio of Ephesus). While this is happening, rumors begin circulating that the Ephesians have escaped. The Syracusians, fearful of being caught, hide in an abbey.
The end of the day approaches. Adriana appeals to Duke Solinus for help for her husband. Meanwhile, Antipholus and Dromio of Ephesus escape their restraints and arrive at Egeon's trial where the Duke sits. Egeon thinks he recognizes them as the son and servant he raised after the storm took the other members of his family. Solinus summons the Abbess, who arrives with the Syracusian twins who had been hiding in the priory. The abbess reveals that she is actually Emilia, Egeon's wife, who had entered the abbey after the storm, presuming everyone else in her family dead.
The play concludes with the Duke pardoning Egeon, who leaves to celebrate with his wife Emilia. Antipholus of Syracuse attempts to pursue Luciana, and the two Dromio twins exit holding hands.