The novella begins with the narrator learning from bar proprietor Joe Bell that their mutual friend Holly Golightly—not heard from in years—apparently attracted some attention as a tourist in Africa not long ago. This news inspires the narrator to recount his knowledge of and experiences with Holly. 

In a flashback, the narrator and Holly meet after the narrator moves into the New York City brownstone apartment building where Holly lives. During their first in-depth conversation, Holly tells the narrator how she is paid to visit an inmate named Sally Tomato in Sing Sing prison every week and then to deliver a “weather report” to a man who claims to be Sally’s lawyer. Holly invites the narrator to a party where he meets a talent agent, O.J. Berman, and the man Holly is romantically involved with, Rusty Trawler. Holly’s friend Mag Wildwood crashes the party and has an emotional breakdown after Holly lies to the men about Mag having a venereal disease. Nonetheless, Mag moves in with Holly and the two form a social circle with Rusty Trawler and Mag Wildwood’s boyfriend, the Brazilian diplomat José Ybarra-Jaegar. At Christmas, Holly gives the narrator an antique bird cage he pointed out to her in a store window. The narrator, in turn, gives Holly a St. Christopher’s medal he purchased at Tiffany’s, the famous New York jewelry store that for Holly symbolizes domestic security and comfort.  

When Holly, Rusty, Mag, and José go on a holiday together, Holly and José grow closer. The narrator and Holly have a falling out after Holly insults his writing. The narrator tries to give the bird cage back but retrieves it after Holly leaves it out with the trash. Holly and the narrator avoid each other for a long time. During this interval, a downstairs neighbor of Holly’s, Madame Spanella, circulates a petition among the building residents, urging them to join her in having Holly evicted for noisy all-night gatherings and unspecified “morally objectionable” behavior. The petition fails.

One day, the narrator notices an older man examining Holly’s mailbox. Eventually the two men end up talking at a diner. The older man introduces himself as Doc Golightly, a veterinarian from Texas, who married Holly when she was fourteen. Doc recounts how one of his children found Holly – who went by the name Lulamae Barnes – and her brother Fred stealing food from his farm to get by, how he took them in to live with his children, and how Holly eventually ran away. He says he came to bring Holly home and has the narrator bring him up to see Holly. Holly greets Doc affectionately but insists on staying in New York. Wishing her luck, Doc leaves without her.

Some time later, the narrator sees a newspaper headline announcing Rusty Trawler’s engagement to Mag Wildwood. When the narrator returns home to the brownstone, he hears a commotion in Holly’s apartment. He arrives there at the same time as José and a doctor. Together, they discover that Holly has wrecked her apartment. After the doctor gives Holly a sedative and she falls asleep, the narrator learns from José that Holly received a telegram from Doc informing her that Fred has been killed in combat. 

José moves into Holly’s apartment, and Holly begins to learn how to cook and speak Portuguese. She also announces that she is pregnant and that she and José will be moving to Brazil together. The narrator is upset by this news, but he and Holly resume spending time together. One day, Holly invites the narrator to go horseback riding in Central Park. The outing takes an unhappy turn, however, when a band of boys deliberately startle the horses, causing the narrator’s horse to bolt. Holly gives chase and, with the help of a policeman (also on horseback), brings the narrator’s horse to a stop in front of a crowd. After the narrator feels faint and falls off the horse, Holly takes him back to the brownstone in a taxi. 

Later that day, photos of Holly are plastered across newspapers with headlines announcing that she has been arrested in connection with a narcotics-smuggling scandal. The “weather reports” Holly was passing from Sally Tomato to Oliver O’Shaughnessy were coded instructions from Sally on how to run the smuggling operation. The narrator then recounts how two detectives burst in on Holly, who was attending to the injured narrator in his bath, and arrested her. The narrator talks to Joe Bell and tries to figure out whom to call to help get Holly released. He tries calling Mag, but she threatens to sue him if he tries to associate her and Rusty with Holly. The narrator eventually calls O.J. Berman, who bails Holly out.

The next day, when the narrator checks on Holly’s apartment to see if she has returned yet and to feed her cat; he finds a man claiming to be José’s cousin collecting José’s things. The man gives the narrator a letter from José, addressed to Holly. The narrator later goes to visit Holly in a hospital room, where she informs him that she miscarried and almost died. Holly has the narrator read José’s letter out loud. In the letter, José explains that he is breaking off their engagement because the scandal of her arrest threatens his family’s reputation and his political career. Holly decides that she is still going to fly to Brazil, despite protestations from the narrator that she will get into big legal trouble for doing so. Holly explains that the police want her to testify against Sally Tomato but that she never will, because even though he may have used her, he treated her kindly.

Holly has the narrator retrieve her stuff from her apartment in preparation for her departure to Brazil. He brings her belongings and cat back to the bar, where Joe voices his disapproval but calls a car to bring Holly to the airport. Mid-trip, Holly has the driver pull over to release the cat. Moments later, she regrets her act and goes back for the cat, but it is gone. After the narrator promises to go back to find the cat and take care of it, Holly leaves. Weeks later, the narrator spots the cat in the window of a home where it was taken in. The authorities do not pursue Holly, and the narrator only hears from her once more. He expresses his wish that he could tell Holly that the cat found a good home and hopes that wherever she is, she has too.