The novel begins by introducing us to a teenaged Charles, awkward, mild, dull, and studious. After struggling though primary school and a series of courses in medicine that he finds inscrutable, Charles passes his exams and becomes a doctor. His solicitous mother finds him a wealthy middle-aged wife named Madame Dubuc, and the couple move to a small town called Tostes, where Charles begins to practice medicine.
One night, he receives a call to set a man’s broken leg. During his visit, Charles is enchanted by the man’s daughter, a beautiful, elegant girl named Emma. Not long after, Charles’s wife dies of a nervous ailment, and within a year Charles and Emma are married. Charles adores his new wife, but Emma is soon bored and disappointed. She does not feel anything like the love described in her favorite romance novels, and she blames Charles’s bad looks and dull conversation. Though he is kind, loving, and moderately successful in his profession, she feels that he is not an adequate husband, and spends her days dreaming of a better life – an elegant, refined, exciting life. When she and Charles attend a dazzling ball, Emma’s longings are sharpened and intensified. She becomes thin and listless, and Charles decides to move them to a new town in hopes of curing Emma’s malaise. Around that time, she becomes pregnant and gives birth to girl named Berthe.
Emma and Charles move to Yonville, a little farming town near Rouen. They quickly meet the town’s small cast of characters, who bore Emma – all except Léon, a dreamy clerk who shares her interest in sentimental discussions of music and literature. She and Léon fall in love, but Emma holds him at bay. Soon, he moves to Paris to finish his law degree, and she languishes in his absence. One day, though, she meets a wealthy, aristocratic man named Rodolphe – a womanizer who decides to seduce her. They begin a long, passionate affair, which initially brings Emma a great deal of joy and satisfaction. But Rodolphe does not really love Emma, and begins to tire of the charade of love. He breaks up with her in a letter the day that they had planned to run away together, and Emma is miserable and delirious for months. Meanwhile, she is racking up very large debts buying pretty clothes and gifts from the sly Lheureux, the town draper. Meanwhile, she and Homais, the town pharmacist, convince Charles to perform a dubious operation on Hippolyte, the stableman at the inn, and the man ends up losing a leg.
One day Charles and Emma travel to Rouen to attend a play. They run into Léon, who has returned from Paris, and Emma and Léon finally strike up an affair. By pretending to take piano lessons, Emma manages to come to town once a week to see him. As with Rodolphe, the affair is joyful at first but eventually becomes repetitive and boring, and both lovers grow dissatisfied with one another.
Emma’s debts grow larger and larger, and one day she receives an official notice stating that she must pay a very large sum of money or forfeit all her possessions. In desperation, Emma tries to get the money from Léon, who is noncommittal; from the town lawyer, who propositions her; and finally from Rodolphe, who refuses her coldly. Emma is wild with confusion and fear. She convinces Justin, the pharmacist’s assistant, to lead her into Homais’s laboratory, and she eats a fistful of arsenic. She dies horribly later that night.
Charles is miserable with grief, and overwhelmed by Emma’s debts. Some time after the funeral he finds Emma’s love letters, and dies only a few days later. Berthe goes to live with a poor relative, who sends her to work at a mill.