Breakfast at Tiffany's is the story of Holly Golightly, a hill-billy turned Manhattan playgirl, and the eclectic circle of friends who surround her. The unnamed narrator of the story is a young writer from a small town, out on his own for the first time. He lives in a New York brownstone and dreams of literary success.

The narrator tells his story in flashbacks, occasionally interjecting comments from his older self. It's clear that even in the present he still thinks about Holly and wonders where she is and what she's doing. There's a feeling of nostalgia in the way he tells the story, as if he were recalling some of the best days of his life.

Before the narrator becomes a close friend of Holly, he is intrigued with her. He can't tell by looking at her whether she is 16 or 30. Men can't help falling in love with her, but she doesn't seem to become really attached to any of them. She throws wild parties in her apartment and takes money from the men who love her. Yet she also has a maternal, caring side to her. She takes care of people and judges them only by the way they treat her. Holly is in a constant state of flux. There is no furniture in her apartment, and most of her belongings are in boxes. She has a cat that she refuses to name and she cannot bear the thought of putting down roots.

Holly visits a man in Sing Sing named Sally Tomato. Tomato's lawyer pays Holly to visit him and deliver and receive messages. Because Mr. Tomato is so kind to Holly, she thinks nothing of this. She assumes he is a lonely old man who just wants some company. The narrator warns her that there could be serious legal ramifications about this, but she doesn't listen to him.

Holly is quite elusive about her past, speaking only of her brother Fred who is in the Army. One day, the narrator sees an older man haunting the brownstone and discovers that this man is Holly's husband. She married him in Texas when she was fourteen years old. Holly gently tells her husband, Doc Golightly, that she can't be with him anymore, and sends him on his way.

Soon after, Holly receives a telegram from Doc informing her that her beloved brother Fred has been killed in the war. She loses control, smashing everything in her apartment, and a doctor comes and gives her a shot that makes her go to sleep. After this episode, Holly settles down. She stays at home, cooks, puts on weight, and buys some furniture. She plans to marry Jose, a Brazilian man of her acquaintance, and she begins making plans.

One day, Holly is arrested for being involved in an international drug ring. The mastermind is Sally Tomato, and Holly has been assisting in the drug ring's communications. Jose cannot bring himself to marry a woman who is a criminal; he's a politician in Latin America. He leaves her without saying good-bye. The narrator, ever loyal, helps Holly to flee the country. She doesn't want to stay in a place where people think ill of her, and she has a free plane ticket to Brazil. The narrator later receives a postcard from Buenos Aires. He promises to find the cat, which finds a permanent home in the Spanish Harlem.