The story is set in Rome around the year 1750.
Act One
Scene One: Don Pasquale's Estate.
Rich nobleman Don Pasquale da Corneto is ill, old, and infirm. Yet, it is not just illness that troubles him—his sole nephew and heir, Ernesto, is in love with the young widow Norina and intends to marry her. To prevent this union, which would tarnish the noble title, Don Pasquale decides on a drastic measure: to marry himself and thus deprive his nephew of any hope for the inheritance. At last, the long-awaited Doctor Malatesta, Pasquale's confidant and friend, arrives. The bride has been found; he reports. Young and beautiful, modest and pious, sensible and kind, she is also a convent-educated protegée of the doctor and his own sister. The old bachelor's joy knows no bounds. Now he will teach the stubborn young man a lesson!
Upon learning of Don Pasquale's plans, Ernesto falls into deep despair: at his uncle's behest, he is ruined and forced to leave his family home.
Scene Two: Norina's House.
Norina is saddened by Ernesto's farewell letter. But is it worth such despair? Together with Doctor Malatesta, she devises a cunning plan to get back at Don Pasquale: posing as Sofronia, Malatesta's sister, Norina is to enchant the old man, marry him, and then teach him a lesson so he forever abandons the idea of marriage.
Act Two
Don Pasquale's Room.
The long-awaited moment has arrived: the bride is in Don Pasquale's house. He is struck by Sofronia's innocence and meekness and wishes to marry immediately. It turns out that a notary is already waiting in the anteroom, ready to draw up the marriage contract on the spot.
The unsuspecting Ernesto appears. He almost foils Malatesta's plan, but the doctor inducts the impassioned lover into his scheme.
The marriage is consummated! But what has happened to Sofronia? She instantly transforms from an angel into a fury and, most horribly, begins to boldly dispose of the estate that the husband has just transferred to his young wife, against his will. Don Pasquale's despair knows no bounds.
Act Three
Scene One: Don Pasquale's Room.
Don Pasquale is beside himself with offence and anger: on the very first day of marriage, his wife went to a ball, leaving her "beloved" husband with a slap. He will settle scores with the vile girl! He will throw her out, he will… Suddenly, the old man's gaze falls on a piece of paper. Oh, horror! It's a love letter. That's it! His patience has overflowed. The bonds of marriage are unbearable, and they must be severed right now, today. The "faithful friend" Malatesta comes to the rescue once again. They devise a plan to expose the treacherous Sofronia.
Scene Two: The Garden.
Don Pasquale triumphs: his wife is caught red-handed at the scene of the crime! Now, for the sake of divorce, he is willing to do anything, even consent to Ernesto's marriage to Norina. But what is this? Norina and Sofronia are one and the same? Don Pasquale realizes he has fallen into his own trap. He is compelled to bless the union of Ernesto and Norina and remain a bachelor forever.