The action of the play can only take place because the two twins are separated as children. The chorus explains that the father lost his son in a large crowd. They tell viewers, "When he came to Tarentum, it happened that there were games afoot: amongst the crowd of visitors the boy went astray from his father." The father is inconsolable with grief and eventually dies. The second twin is renamed Menaechmus in his brother's stead. The first twin is adopted by a merchant from Epidamnus and grows up wealthy.

The first Menaechmus is married but has taken up with Erotium, whom he claims to prefer. In retaliation for his wife's anger, he takes her cloak to give to Erotium. He says, "We that have loves abroad and wives at home, are miserably hampered, yet would every man could Tame his Shrew as well as I do mine. I have now filched away a fine cloak of my wife's, which I mean to bestow upon one that I love better." The cloak is a major factor that helps drive the mistaken identities later in the play, as the wife and Erotium both mistake one brother for another and try to give or take the cloak to or from the second Menaechmus.

The second Menaechmus is running out of money, and his slave, Messenio, encourages him to give up the search. He refuses, though. He is committed to finding his brother no matter what it takes. They speak:

Menaechmus: Till I find my brother, all towns are alike to me: I must try in all places.

Messenio: I think if we had sought a needle all this time, we would have found it, had it been above ground. It cannot be that he is alive; and to seek a dead man thus among the living, what folly is it!

Menaechmus. If I could find any man that could certainly inform me of his death, I would be satisfied. But otherwise I can never desist seeking. Little you know, Messenio, how near my heart it goes.

Even though others have given his brother up for dead, he is unwilling to. This is why he has spent all his money and traveled the globe to find him. During this discussion, he does not yet know that he is finally arriving in the right place.

The first case of mistaken identity is between the second Menaechmus and Erotium's cook, Cylindrus.

Menaechmus: You show you have your wits to call me so; but tell me, where do you know me?

Cylindrus: Where? Even here, where you first fell in love with my mistress Erotium.

Messenio explains this by saying the city is full of scammers who've learned their names to take their money. This scene also lets the audience know how alike the two twins appear.

The second Menaechmus decides to play along with Erotium and let her think he's someone else. He says to Messenio, "Why so? I warrant you, I can lose nothing; yet something I shall gain; perhaps a good lodging during my abode here. I'll dissemble with her a little while." Then he says to Erotium, "Now when you please let us go in. I made strange with you, because of this fellow here, lest he should tell my wife of the cloak which I gave you." This helps further her belief that he is her lover, the original Menaechmus.

Menaechmus's wife finds out that he's been unfaithful because Peniculus mistakes the second Menaechmus for the first and believes he was not invited to dinner at Erotium's. He says,

"Not a...