The Goldfinch is told in retrospective first-person narration by Theodore "Theo" Decker, who recounts the story of his life thus far. As a thirteen-year-old boy in New York City, Theo adores his energetic, beautiful mother — as do many other people in Manhattan. He thinks of his father, who had walked out on them a year earlier, as an alcoholic, abusive thief. Theo's life is turned upside down when he and his mother visit the Metropolitan Museum of Art to see an exhibition of Dutch masterpieces, including her favorite painting, Carel Fabritius's The Goldfinch. There, he falls in love at first sight with a red-headed girl who is accompanied by an elderly man. But then a terrorist bomb kills his mother and dozens of other art-loving citizens.
In the rubble, Theo encounters the old man, Welton "Welty" Blackwell, who gives him a ring and an enigmatic message. Believing that Welty is pointing at The Goldfinch, Theo takes it during his panicked escape. The taking of these items (one a family heirloom handed over freely, the other a priceless and famous art work) is done by Theo in a state of terror, concussion and shock, and he has no understanding of how these seemingly minor actions will influence the rest of his life.
Alone and determined to avoid being taken in by the city as an orphan, Theo lives with a school friend, Andy Barbour, and his wealthy family (Mr. Barbour, a pleasant man as long as he takes his prescribed medication; Mrs. Barbour, a seemingly chilly but kind socialite who likes Theo; Platt, the oldest son, a boarding school bully; Andy, 14, a genius nerd; Kitsey, 9, "a candyfloss Disney Princess"; and Toddy, the youngest). Theo lives in the Barbours' elegant house for several months and is fairly happy there (despite his continuing nightmares and posttraumatic stress disorder). Unbeknownst to the Barbours, Theo carries out the last wishes of Welty and returns the ring to his family, becoming friends with James "Hobie" Hobart, Welty's partner. He also briefly encounters the red-haired girl, Pippa, who was injured in the bombing and is being sent to live with relatives in Texas. Theo feels an intense bond with her but fears he will never see her again.
Theo's life with the Barbours is shattered when his deadbeat dad, Larry Decker, arrives with his new girlfriend, Xandra, and whisks him away to Las Vegas. Theo secretly brings the painting, afraid to tell anyone about it for fear he will get in trouble.
In Las Vegas, Theo feels rootless and his father and Xandra make little effort at parenting. His father earns a living and pays for a large home outside Vegas with gambling wins. At school, Theo makes a new friend, Boris, a cosmopolitan son of a Ukrainian émigré. The two boys both have absentee parents and spend most of their afternoons drinking alcohol, feeding themselves from shoplifted store groceries, using marijuana and other illegal drugs, talking from night to dawn, and giving friendship to Popper, Xandra's neglected Maltese puppy.
Over time, Theo's father starts to become more friendly and even asks for Theo's social security number in order to open a savings account to help him in the future. But it later becomes apparent that his father has ulterior motives — he is in debt to a crime syndicate and one day begs Theo to phone his mother's lawyer in New York to get access to money she had put aside for Theo's education. The lawyer, Mr. Bracegirdle, smells a rat and refuses to release any funds, indirectly revealing that his father had already tried using Theo's social security number and forging his signature to steal the money. Humiliated and desperate, Theo's father gets drunk and dies in a car crash.
Theo knows he must leave town at once, or be sent to a Nevada care home. He and Boris steal some money and drugs from Xandra. Boris begs him to stay one more day, but Theo wants to return to New York, and his friends, that minute. When his pleas go unheard, Boris kisses Theo and lets him go. He packs his stuff, including the package containing The Goldfinch, and leaves. After a bus ride across the country, filled with tension because Theo has decided to bring Popper, Theo returns to New York. He sees Mr. Barbour on the street, but Barbour (no longer on his medications), acts wildly and shuns him, so he can think only to go to Hobie's door. Pippa is there, as well as Hobie, and they welcome him and give him a place to stay. Pippa is only visiting, as she is at a school in Switzerland for disturbed girls, and so Theo is forced to say goodbye to her once more.
Theo's narrative now skips ahead eight years. Theo has become a full partner in Hobart's antiques and furniture-repairing business. He has concealed The Goldfinch in a storage unit because the news is full of stories about the prosecution of thieves who stole from the museum after the bombing, and he is afraid of being accused of theft. He is still in love with Pippa, but she treats him only as a close friend and is living in London with a boyfriend. He has instead formed a relationship with Kitsey Barbour, and they are planning to marry.
Theo has gotten himself into trouble, however. He is addicted to prescribed medications, which he buys on the street. He has saved Hobie from bankruptcy, but has done so by selling fake antiques (which Hobie had created for fun and had never intended for sale). Now, one of those buyers, Lucius Reeve, is attempting blackmail. Reeve has figured out that Theo was in the same museum room with The Goldfinch during the bombing and believes Theo and Hobie know its whereabouts. He threatens Theo with the consequences of revealing this information; Theo is afraid not only for himself but also for letting down the innocent and trusting Hobie.
Theo is racked by guilt and fear over the fakes and The Goldfinch. Then, a series of dramatic events take place in short succession. Theo learns, on the day before their engagement party, that Kitsey has never stopped loving Tom Cable, a criminal teenager with whom Theo attended high school, and they have an inconclusive argument about it. Boris then reappears in Theo's life, now a wealthy man on the proceeds of various dubious and unspecified activities. To Theo's astonishment, Boris reveals that he had stolen The Goldfinch from Theo while they were in high school and swapped it for a textbook of similar weight; the painting has since been used as an object of barter by various criminals and dealers. Boris feels guilty and has devoted himself to recovering the painting and returning it to Theo. The stunned Theo returns home to find Pippa unexpectedly staying there due to a cancelled flight. They go out to see a movie and have dinner, and Theo enjoys his rare time alone with her, even though it is clear by the end of the evening that Pippa feels pity for him rather than love.
At Theo and Kitsey's engagement party, Boris suddenly appears with a plan to return The Goldfinch to Theo. The plan involves flying to Amsterdam and meeting with men who are holding the painting. Theo, in a state of panic due to the presence of an associate of Lucius Reeve at the party and his anger over Kitsey's deceptions, agrees to walk out without telling anyone where he is going, leaving Pippa a note saying he loves her and a ludicrously expensive necklace as a Christmas present. In Amsterdam, Boris and his henchmen show up with guns and, at the meeting with the dealers, attack them and steal the painting, dragging the shocked Theo with them. Boris is very pleased with himself, but they are then hunted down by agents of the dealers and in a shootout, Boris is shot in the arm and Theo shoots the killer, while a boyfriend of one of the dealers escapes with the painting.
Leaving the injured Boris, the devastated Theo holes up in his Amsterdam hotel room taking drugs. His phone dead, convinced he is about to be arrested, and unable to travel having left his passport with the vanished Boris, he feels trapped, and contemplates suicide. But after several hellish days, Boris returns, and reveals that he has saved the situation by phoning the art recovery police to inform on the dealers. Not only has the painting been saved for the museum, but Boris has even received a huge reward, which he shares with Theo. He returns to New York to face the angry and devastated Hobie, who has learned the full details of Theo's selling of the fake antiques. Theo explains everything to Hobie, including The Goldfinch, which, Hobie reveals, was Welty's favourite painting too.
The novel ends with Theo travelling the world to put things right by buying back the fake antiques that he had sold. His relationship with Kitsey remains ambivalent, and Pippa has told him that she does feel love for him but that their character flaws are too similar for them to be safe together. In a lengthy reflection on what he has learned from his experiences, Theo wonders how much of his experiences were unavoidable due to fate or his character. Finally, he contemplates The Goldfinch and of "the history of people who have loved beautiful things, and looked out for them, and pulled them from the fire".