Moschus has twin sons, Menaechmus and Sosicles. Moschus decides to take only one of the twins, Menaechmus, with him on a business trip, while the twins are still young. During the trip, Menaechmus is abducted and adopted by a businessman who lives in Epidamnus, separating the twins. Their father dies of sorrow and their grandfather changes Sosicles' name to Menaechmus (i.e., Menaechmus of Syracuse). When the twins are grown to manhood, Menaechmus of Syracuse sets out in search of his brother. He arrives in Epidamnus, unaware that his twin brother is there also.
Here, the brother is first shown to be, with good cause, the despair of his jealous wife. He is seen leaving his house, berating his spouse as a shrew and a harpy, promising that she shall have good cause for her jealousy. He confides to Peniculus, a professional parasite, that he has stolen his wife's mantle and is going to give it to Erotium, a prostitute who lives next door.
The two go to Erotium's door, and the husband presents the mantle with many blandishments. He suggests that a fitting return would include a dinner for himself and Peniculus. Erotium agrees, and the two men go to the Forum for preliminary drinks while the meal is being prepared.
Meanwhile, the twin from Syracuse has arrived with Messenio, his slave. The latter warns him of the depravity of Epidamnus, urging an end to the search for his missing brother since their money is nearly gone. His master gives his purse for safekeeping to the slave who continues his warning against the cunning people of Epidamnus "who think nothing of accosting a stranger" and bilking him of his money, when Erotium steps out of her house and endearingly accosts the Syracuse Menaechmus, thinking him to be his brother.
She asks why he hesitates to enter when dinner is ready, and the confused twin asks her, quite formally, what business he has with her. Why, the business of Venus, Erotium replies coyly. Messenio whispers to his master that the lady undoubtedly is a schemer for his money, and asks her if she knows his master. He is Menaechmus, of course, replies Erotium. This amazes the twin, but Messenio explains that spies of the city's thieves probably have learned his name.
Erotium, tiring of what she considers foolery, tells Menaechmus to come in to dinner and bring Peniculus. Peniculus, he answers, is in his baggage—and what dinner is she talking about? The dinner he ordered when he presented his wife's mantle, she replies. He first protests vainly that he hasn't any wife and has just arrived in the city, then begins to realize the possibilities of a dinner and a pretty girl. He sends Messenio to the inn, giving him orders to return for his master at sunset.
After the meal, he leaves his house with a garland on his head and the mantle over his arm; Erotium has told him to have it re-trimmed. He is chuckling over his luck—dinner, kisses and an expensive mantle—all for nothing, when the irate Peniculus, who has lost the Epidamnus twin in the Forum crowd, meets him and berates him for dining before he could arrive. Quite naturally treated as a stranger, Peniculus angrily rushes to tell the other twin's wife of the stolen mantle.
The Syracuse brother, further baffled because the unknown Peniculus addressed him by his name, is pinching his ear to make sure that he is awake when Erotium's maid comes out and hands him a bracelet to be taken to a goldsmith for repair. He suspects that something is amiss, and hurries off to the inn to tell Messenio of the happy shower of valuables that has been raining upon him.
Now the furious wife, told by Peniculus of her man's trick, rushes out of her house just in time to meet her husband returning from the Forum, expecting Erotium's banquet. She tells him to return the mantle or stay out of her house, and the husband goes to Erotium to get it, resolving to buy his sweetheart a better one. He is stupefied when she declares him a liar and a cheat, and tells him that she has already given him both the mantle and her bracelet. So the Epidamnus twin finds the doors of both his wife and mistress slammed in his puzzled face, and goes off to get the counsel of his friends.
The Syracuse Menaechmus returns, the mantle still over his arm, in search of Messenio, who has left the inn. His brother's wife sees him, and assuming him to be her husband, demands that he confess his shame. He asks her of what he should be ashamed—and, furthermore, why she should address a total stranger so. He adds that he didn't steal her mantle, that a lady gave it to him. This is too much for the wife, who calls her father from the house. The father, also assuming that he is the husband, tells him that he must be crazy. This idea seems an excellent means of escape for Menaechmus: he feigns insanity so violently that the father rushes off for a physician, the wife seeks safety in the house, and Menaechmus goes off to resume his hunt for Messenio.
As the father comes back with a doctor, the real husband returns. He flies into a rage when his wife and father-in-law add to his troubles by implying that he is quite mad. His anger convinces the doctor of his insanity, and he summons slaves to bind him and take him to an asylum. Just then, Messenio appears, and, thinking the struggling husband his master, overpowers the slave. As a reward he asks for his own freedom. The husband tells Messenio that he doesn't know him, but by all means to consider himself freed; then he begins to suspect he may really be a bit crazy when Messenio tells him that he will return shortly to give him the money he has been safeguarding. Husband Menaechmus is not too addled, however, to profess his ownership of the purse.
The husband goes to Erotium's house in further search of the mantle. The Syracuse twin returns, in his quest of Messenio, at the moment when the servant hurries back with his purse. His master upbraids him for having been gone so long, but the slave protests that he has just saved his owner from ruffians and has been set free. The master is pondering this new muddle when his twin appears from Erotium's house.
The two brothers rub their eyes in bewilderment on seeing each other, but explanations quickly bring recognition. They embrace. The happy master truly sets the slave free, and the brothers decide that the first Menaechmus shall go to live with his twin in Syracuse. Messenio announces an auction in the morning of the husband's goods, everything to go to the block—even the wife, if there be a buyer.