Ephesus and Syracuse are at odds. Any Syracusan found in Ephesus will be executed unless he can pay a ransom of a thousand marks. Egeon, an old Syracusan merchant, has been arrested. He explains how he has come to Ephesus: he and his wife Emilia had identical twin sons and identical twin slaves, purchased for the purpose of serving the sons. In a shipwreck many years ago, he was separated from his wife, one son and one slave. The survivors are renamed in memory of the lost ones: Antipholus for the son and Dromio for the slave. Once grown to manhood, Antipholus of Syracuse, with his Dromio, had set off in search of his brother and mother. Egeon is now in search of them. The Duke gives him until evening to find the ransom money. By chance Antipholus and Dromio of Syracuse have also just arrived in Ephesus. The other Antipholus and Dromio have been living there since the wreck. And so the comedy of errors ensues. The locals constantly mistake the visiting twins for the natives - even Antipholus of Ephesus' wife Adriana and her sister Luciana are fooled. The confusions result in Antipholus of Ephesus being arrested for debt and declared mad, while Antipholus of Syracuse take refuge from his brother's angry wife in a Priory - where the abbess turns out to be Egeon's long-lost wife. All is resolved and Egeon is freed.
The play was written to argue to Elizabeth for reinstatement to court in 1583. The play apologizes for de Vere's errors in matrimony.
The play is about marriage into a powerful family - a marriage that never should have been. De Vere is the misunderstood husband Antipholus of Ephesus, married to a "fond fool" of an impatient wife Adriana. Antipholus has a twin brother Antipholus of Syracuse that he does not know. He falls in love with Luciana, the placid and idealized sister of Adriana. De Vere splits both the character of himself and his wife. Anne Cecil's character is divided between Luciana (= the light one) and Adriana (= the dark one). De Vere's character is split between two protaganists. The marriage was unsuccessful because it united his bride with only half his self. The Duke of Epheseus observes of the twin brothers:
One of these men is genius to the other;
And so of these, which is the natural man,
And which the spirit? Who deciphers them?
The play reveals de Vere at the time as an overgrown adolescent unwilling to shoulder responsibility for his failed marriage. The play is an attempt to explain and excuse his errors, but does not acknowledge fault.
Elizabeth is portrayed as the fat kitchen wench Nell.
ANTIPHOLUS OF SYRACUSE: What's her name?
DROMIO OF SYRACUSE: Nell, sir; but her name and three quarters, that's an
"el" and three quarters (=syllables), will not measure her from hip to hip.
ANT. In what part of her body stands Ireland.
DRO. Marry, sir, in her buttocks, I found it out by the bogs.
ANT. Where Scotland?
DRO. I found it by the barrenness, hard in the palm of the hand.
ANT. Where France?
DRO. In her forehead, arm'd and reverted, making war against her heir …
ANT. Where stood Belgia, the Netherlands?
DRO. O, sir, I did not look so low.
In 1563, William Cecil hired Laurence Nowell to tutor de Vere, whose father had recently died and who was now under the wardship of Cecil. Nowell was a cartographer, who at the time was working on the most detailed map of the British Isles known to that time. The map can now be found in the British Library as an example of Renaissance cartography. The map may have inspired a series of cartographical jokes in the play about maps of England, Ireland, and other nations.