The novel opens in New York during World War II. We're introduced to an unnamed narrator who moves into a brownstone apartment building in the city in order pursue his career as a writer. Shortly after moving into the apartment, he sees Holiday Golightly (she goes by Holly for most of the novel) for the first time late one night in the hall of the apartment building, but it takes a while before he actually meets her face-to-face.
And then one night his life changes entirely when Holly knocks on his bedroom window after she's been sitting out on the fire escape watching him. He lets her in and after the two get to know each other a little better, Holly crawls into the narrator's bed (just so she can get some rest) because he reminds her of her brother Fred and she feels safe with him. But when she starts crying, and when the narrator asks her about it, Holly rushes back to her own apartment (and we and the narrator learn that Holly doesn't like discussing anything too personal about her life).
Holly and the narrator start to spend some time together, and he learns that Holly is in the habit of entertaining lots of different men at loud parties in her apartment. He's invited to one of these parties and, among others, meets a Hollywood agent named O.J. Berman, who once tried to get Holly into movies, and a man named Rusty Trawler, who pretends he loves Holly but who she thinks is actually gay. The narrator also meets Mag Wildwood at one of these soirees (she's a model who can't hold her liquor and who Holly doesn't like very much). Mag is engaged to a Brazilian diplomat named José Ybarra-Jaegar (he becomes important to the story a little later on).
One of the ways Holly earns money is by visiting alleged mobster Sally Tomato in prison every week. The visits seem innocent enough, and Holly gets paid to send weather reports back to Sally's lawyer (whose name is O'Shaughnessy). But we soon learn that these weather reports aren't as innocent as they seem.
At some point, Holly, Rusty, Mag, and José take a trip to Florida, and after Mag and Rusty both end up in the hospital, Holly and José start an affair with each other that ends up with Holly getting pregnant. Mag and Rusty find out about the affair and marry each other instead (the marriage ends badly, we later learn). Does this sound enough like a soap opera yet? Wait, there's more!
José eventually proposes to Holly and she makes plans to move to Brazil to be with him. This devastates the narrator, who has fallen a little in love with Holly and who has come to depend on having her in his life. But he agrees to go horseback riding with her in Central Park a few days before she's scheduled to leave New York so she can say good-bye to her favorite horse. The ride is a disaster in more ways than one. The narrator's horse freaks out and takes off with the narrator still on him. So Holly rides hard to catch up to the narrator and to save him, an overexertion that causes her to lose the baby (though we don't know that yet).
Later the same evening, Holly is tending to the narrator, who is still sore and battered from the horseback ride, when she's confronted by two detectives who arrest her for being part of a drug ring headed by Sally Tomato. It seems those weather reports were actually messages about drug shipments (which Holly is unaware of), and she's taken into custody and her name is splashed all over the evening newspapers. José loves Holly, but he decides that he can't risk being associated with any scandal since it could ruin his political career. He writes her a "Dear John" letter and returns to Brazil without her (keep in mind that he thinks she is still pregnant with his child).
Since Holly no longer has married life with José to look forward to, she decides she's going to leave the country (even though she's still under investigation for the drug charges), and decides she's going to head to Brazil anyway since José has already paid for her ticket. She asks the narrator to help her gather her things since she's being watched by the authorities (which he does), and she eventually makes it to the airport and goes on her way.
A lot of time passes before the narrator hears from Holly, but he finally gets a postcard from her. It seems she's made her way to Buenos Aires where she's fallen in love with a rich (and married) man. She promises to write the narrator again once she has a permanent address, but we learn that he never hears from her again and he's left wondering what becomes of her and whether she ever finds happiness.