Florentino decides that he will win fame and fortune while he waits for Dr. Juvenal Urbino to die, so that he can have Fermina Daza in the end. To accomplish this goal, he goes back to Don Leo XII Loayza for a job and gets appointed clerk to the Board of Directors because of his reputation for reading and writing. He turns out to be incapable of writing business letters because his sentimentality and lyricism make his letters worthless for business. He does his best to learn to write without romance, but he finds it so exhausting and emotionally stifling that he goes daily to the Arcade of the Scribes to write love letters for others.
Two of his customers are writing letters to each other. Once they are happily married and realize that Florentino Ariza was essentially writing love letters to himself for them both, they ask him to be their first child's godfather. Florentino's friends notice that he is changed. Winning back Fermina becomes the sole focus of his changed life.
He is so sure of his ultimate success that Transito Ariza buys their house and renovates it to be fit for Florentino to bring Fermina when the time comes. While redoing the house, Transito shows early symptoms of the memory loss that will mature into the disease that will eventually kill her. Meanwhile, Florentino's new sense of responsibility has its limits: he begins his hunting for women, taking them at first to the transient hotel, but then just loving them wherever he can. Still, he never takes them to his house, keeping it sacred on behalf of Fermina; to have sex there with other women would be the real unfaithfulness.
Florentino uses the trolley as a place to find women. During Carnival he meets a woman who brings him back to the innocence he had before Fermina broke his heart, and he falls in love with her. At the end of the night, just as he is about to take her off somewhere, she is captured by two guards and a nurse from the Divine Shepherdess Asylum, where the woman was a patient--she had just decapitated a man while escaping. Florentino is heartbroken and for months walks by the asylum with a box of chocolates in the hope that she will look out the window.
Florentino also meets Leona Cassiani on a trolley. He is certain that she is a whore, so even though he is very attracted to her, he decides not to pursue her because he will never pay for sex. But she follows him, and it turns out that she wants him to get her a job at the River Company of the Caribbean. Florentino, feeling guilty for assuming she was a whore, gets her a low-level job. She eventually rises toward the top, pushing Florentino up ahead of her.
After ten years, when he finds himself alone with her in the office, Florentino finally tries to seduce her, but she tells him he is too late for she has committed too many dirty tricks for his benefit to now sleep with him. They continue, however, to be close friends who love each other deeply. Florentino finds himself tempted to tell Leona about his enduring love for Fermina, feeling crushed by the secret that only his mother knows.
One day, Dr. Juvenal Urbino comes to see Don Leo and waits for him in Florentino's office. Dr. Urbino discusses his civic endeavors with Florentino, and while doing so he mentions Fermina in such a way that it becomes clear to Florentino that Dr. Urbino loves his wife almost as much as Florentino does. Florentino also feels sad, for the first time, that Dr. Urbino will need to die before Florentino can be happy. After this meeting Florentino almost tells Leona about his love for Fermina, but when she fails to pick up his hints he lets the issue drop. He realizes that he will be able to tell Fermina that he never revealed their secret to anyone if he does not tell Leona.
At the first Poetic Festival, Florentino meets Sara Noriega, who shows sincere grief for Florentino when he does not win. This begins another of Florentino's extended affairs. He keeps this one clandestine, too, although neither he nor Sara Noriega is committed to anyone else. Florentino still imagines himself being completely loyal to Fermina, so he cannot risk having his numerous relationships known. This has resulted in many people believing that there is something wrong about him, or that he is homosexual.
For the fifth Poetic Festival, Florentino and Sara Noriega write a poem together, which she is convinced will win. When it does not, she becomes convinced that it is because Fermina Daza is against her, so she speaks insults against her to Florentino, saying that Fermina is a whore for marrying a man she does not love for money. From that moment, Florentino can never see Sara in the same way. When he leaves that night, he never returns. During the five years that they were together, though, Florentino was quite happy with her, as close to cured as he ever would be.
Sara was right: Fermina's choice of Dr. Urbino over Florentino really had little to do with love. She first suspected him of being a paternal plot, since her father wanted her to marry him so badly, but even as she grew to like him more, in the end she only accepted his proposal because she thought she was about to lose the opportunity forever. She did not regret their marriage immediately, but she did when they returned home from Europe to live in Dr. Urbino's mother's home. Dona Blanca is so impossible to live with that Fermina becomes desperately unhappy, and she can find solace only in her son. Fermina faces the unhappiness of having her father's suspicious dealings uncovered, and in order to protect the family honor, Dr. Urbino has him sent out of the country.
Fermina finally convinces Dr. Urbino that they need to leave to find their love again, so they return to Europe with their son. Meanwhile, Florentino is working more and more, and his mother is deteriorating to the point that she can no longer recognize him. He spends almost all of his time taking care of his mother and working, and for a period of time he gives up hunting for women--especially after his experience with Olimpia Zuleta.
Florentino meets Olimpia while she is caught outside in a storm, and he drives her home. She is married to a pigeon seller, so Florentino tries to buy one from him, but she gives it to him in thanks. He uses the pigeon to send love notes to Olimpia, who is very slow to be seduced but who allows him to keep trying. Eventually he succeeds, and they make love. He paints markings on her stomach, and when she goes home her husband sees them and immediately murders her. Florentino is horrified and heartbroken. His mother dies around the same time that Olimpia is killed, and Florentino brings roses to both of their graves.
Fermina and Dr. Urbino return from Paris after two years, having heard of Dona Blanca's death. Fermina is pregnant again. She and Dr. Urbino find a peaceful love together, though Fermina is disturbed by the perfection Dr. Urbino continually expects in the household. Yet at this time, after thirty years of marriage, they are happiest together, and they love each other most.
Part four brings back the themes of time and age that were introduced in part one. At the start of the section, Dr. Urbino and Fermina have been married for two years, and by the end of the section they have been married for thirty. Note, however, that there is no consistent chronology in the section, which jumps back and forth throughout this span of twenty-eight years. Both the jumping chronology, which often leaves the reader unsure of the age of the characters in each scene, and the lack of descriptions of the characters having aged until the end of the section, makes the fact that so much time has passed rather shocking to the reader. To readers, as to Florentino, it seems that the characters have gone from their twenties to their fifties in a moment. All this time, despite his other escapades, Florentino has been waiting.
The repetitive nature of Florentino's life in this period makes it seem as though events keep happening but time is not passing. Each of the distinct stories of his love affairs seems to be the same as the others with only slight alterations. This pattern makes it seem that the same events keep happening over and over again as though time is not moving forward but is stalling or going in a circle. This narrative structure similarly highlights how easy it is for time to pass without anyone realizing it. People age gradually until the physical decay of aging makes clear the passage of a great deal of time.
Florentino's sudden realization that thirty years have passed is a shocking reminder of how much he really does sacrifice, at least in his mind, for Fermina. Olimpia ends up giving her life for her one night with Florentino, but Florentino waits his whole life to spend the last small fraction of it with Fermina. This seems to be the first time that he realizes the dire nature of his commitment. As he realizes that thirty years have passed, he questions for the first time his previously firm belief that Dr. Urbino would die before he would. Florentino sees that he is running out of time. And while he has watched his mother decline with age, in general Dr. Urbino and Fermina have increased in the love characteristic of a married couple.
Florentino's fear of death thus has nothing to do with a fear of what comes after death; it is his fear of not having enough time to fulfill the one for which he has lived nearly his whole life. In comparison, note Dr. Urbino's great fear of death in the first part, which is a matter of fearing the unknown. For Urbino, his faith in the religion to which he has spent his whole life closely tied is not enough. Dr. Urbino does not care about time like Florentino does, but he does fear aging and death for their own sakes. Florentino cares about age and death only as symbols of lost time and as evidence of the decline of a person's powers. This is because his life is ruled by love and he needs time to realize that love.