John Dowell, the narrator, promises to tell the saddest story he knows, which revolves around John, his wife Florence, and their friends Edward and Leonora Ashburnham. Both Florence and Edward have heart conditions, so they always spend part of their year in Nauheim, Germany for rest and relaxation. John, Florence, Edward, and Leonora first meet one another while in Nauheim and they quickly become friends. However, before long, Florence and Edward start having an affair. Leonora quickly realizes what is going on, but she does not tell John because he is oblivious, and she doesn’t want to hurt him. Although the affair is hurtful to Leonora, it is not a surprise because Edward has had multiple affairs in the past.
Most recently, Edward attempted to pursue a girl name Maisie Maiden. Maisie is a friend of the Ashburnhams who traveled with them to Nauheim. Leonora knows that Edward is interested in Maisie, but she allows him to pursue her anyway. Leonora is content with this dynamic because she thinks it unlikely that Maisie will give in to Edward. Additionally, even if she does give in, Leonora doesn’t think Maisie will cause problems like Edward’s previous lovers (in the past, Edward got himself involved in several affairs that caused the Ashburnhams legal, social, and financial problems). However, Edward’s pursuit of Maisie comes to a swift end when Maisie discovers that the Ashburnhams brought her to Nauheim so that she could act as Edward’s mistress and is horrified. While packing her suitcase to leave Nauheim, Maisie suffers a heart attack and dies.
John often pauses his narration to think about how cleverly everyone manipulated him, especially Florence. Although the novel takes place in Europe, John and Florence are Americans who married in the U.S. before traveling abroad to Europe. Florence only told John about her heart condition after the two of them were married. According to Florence and her doctors, Florence and John cannot have sex because it would be too much for Florence’s heart. John dutifully obeys the doctor’s orders, only to discover later that Florence faked her heart condition. In retrospect, John spends much of his time coming to terms with the fact that his entire relationship with Florence was a lie.
Florence and Edward continued their affair for some time. However, things get complicated once Edward takes an interest in Nancy Rufford. Nancy is a young woman whom the Ashburnhams practically raised. Now that she is of age, Edward displays a romantic interest in her, much to the chagrin of Leonora. When Florence discovers Edward’s romantic pursuit of Nancy, she commits suicide by poisoning herself. John is the first one to discover her body.
After Florence’s death, John returns to America to settle her estate. Coincidentally, Florence’s Uncle John died just a few days before Florence herself, leaving John a large fortune. After John ties up his financial affairs, he sails to England to visit the Ashburnhams in their manor home. John, too, is romantically interested in Nancy and hopes to ask her for her hand in marriage. Once in England, John discovers that the Ashburnhams’ relationship has continued to devolve. Both Leonora and Edward are physically and mentally ill. Although Edward has stopped pursuing Nancy, he is tortured by the fact that he cannot be with her. Meanwhile, Leonora cannot stand the fact that Edward loves Nancy more than her. Because Edward’s love for Nancy is literally killing him, Leonora goes to Nancy and begs her to be Edward’s mistress. Nancy declines and then leaves for India, not wanting to cause more problems.
On the way to India, Nancy sends the Ashburnhams a letter, letting them know she is safe and sound. Edward reads the letter while alone with John in the Ashburnham’s stables. After reading the letter, Edward pulls out a penknife and slits his own throat. John watches him commit the act and does nothing to try to stop him. After Nancy finds out what Edward did, she is racked with guilt and has a mental breakdown. Because Leonora cannot bear to see Nancy, she asks John to go to her. John does as Leonora asks and travels to India. There, he finds Nancy completely broken down. She is unable to speak or function normally. John thinks it is a bitter irony that, in the end, he is once again acting as a nurse to a woman whom he loves but does not love him back.