The novel begins with a note from Mrs. Basil E. Frankweiler to her lawyer, Saxonberg, requesting that certain changes be made to her will. When Saxonberg reads the following account, she promises, he will understand why.
Claudia Kincaid, almost 12, wants to run away from home. She hates being uncomfortable, though, so she chooses a beautiful place to hide: the Metropolitan Museum of Art in New York City. Claudia is running away because of the “injustice” of having to do chores and be responsible for her three younger brothers. However, she decides she’ll take along nine-year-old Jamie, the second youngest, because he’s “rich” and reasonably quiet. In the meantime, Claudia has to save up enough for round-trip train fare. After her family has “learned a lesson in Claudia appreciation,” she plans to return home.
One Monday after school, Claudia reveals her detailed plan to Jamie. They will run away on Wednesday, music lesson day, so that they can pack extra clothes in their instrument cases without anyone knowing. Jamie agrees to the adventure, though at first, he doesn’t want to tell Claudia how much money he’s saved up—almost $25. He finally admits that he’s earned this money by gambling with his friend Bruce; he always wins.
According to plan, Claudia and Jamie stay on the school bus on Wednesday morning after the rest of the kids have gotten off. After the driver parks and leaves, the kids walk to the train station (Claudia stops to mail a note of explanation to their parents), quarreling on the way. They ride the train from suburban Greenwich, Connecticut to New York City. Jamie isn’t thrilled when he learns they’ll be hiding in the art museum, but when Claudia appoints him their official treasurer, he cheers up.
When they arrive in New York, Jamie insists that they save money by walking to the museum instead of taking the bus or a taxi. Once there, they agree on a plan to hide during the museum’s opening and closing (by ducking into bathroom stalls until the guards have left), and Claudia chooses an antique canopy bed for them to sleep in. Even though they keep arguing, the pair starts to feel like more of a team.
The next morning, the kids hide their belongings—and themselves—until the museum opens. Then, starving, they leave the museum to buy a cheap lunch, and Claudia decides they should devote themselves to learning as much about art as they can—they’ll choose a different gallery to study each day. Jamie chooses the Hall of the Italian Renaissance today, hoping Claudia will get bored and give up. But when they get there, they join a line of over 1,000 people waiting to see a new exhibit. There’s even a New York Times photographer documenting the event. When they reach the front of the line, they see a small, graceful sculpture of an angel. Claudia thinks it’s the most beautiful thing she’s ever seen.
The next morning, Claudia finds a copy of the Times and reads about the “Angel” statue, which might be one of Michelangelo’s early works. It was recently purchased for just $225 from collector Mrs. Basil E. Frankweiler, who bought it in Bologna, Italy before the Second World War. Mrs. Frankweiler, a widow, lives alone on a Connecticut estate. Claudia decides that instead of trying to learn about the whole museum, they should dedicate themselves to learning about this statue and finding out whether Michelangelo really sculpted it. Claudia feels that solving this mystery is somehow important for her future.
The next day, Saturday, Claudia insists on going to the library to research Michelangelo and the Italian Renaissance. The main thing the kids learn is that many of Michelangelo’s works have been lost. That night in the museum, they narrowly avoid crossing paths with workers who are moving the angel statue. While taking baths in the museum’s restaurant fountain, they pick up almost $3 in coins to supplement their disappearing budget.
On Sunday, Jamie and Claudia study Angel before the museum opens. They notice the impression of an M on the velvet underneath the sculpture. Later, they look at books in the museum’s bookstore and confirm that the “M” is Michelangelo’s stonemason’s mark. Sure they’ve found a critical clue, they plan to rent a post office box at Grand Central Station and send an anonymous letter to the museum, sharing their discovery. If the museum writes back asking for help, Claudia and Jamie can become heroes. The next day, the kids look for a visiting school group, hoping they can ask a random student to deliver their letter for them. To their shock, they overhear a group from their own school back in Greenwich. Jamie uses this opportunity to deliver the letter to the museum office himself, pretending he’s part of the field trip.
On Wednesday, Claudia and Jamie find a letter in their P.O. box—it’s from the museum’s Public Relations office. The polite letter thanks them for their tip, but informs them that the museum has known about the “M” for a long time, and it isn’t conclusive evidence—it could mean that Michelangelo merely designed Angel but didn’t carve it, or even that somebody else used Michelangelo’s mark. After reading the letter, Claudia starts to cry. Jamie asks if this means they should go home, but Claudia says she can’t—she’s realized she wants to go home “different,” and she can’t do that without solving Angel’s mystery. When Jamie insists on buying train tickets home, Claudia interjects that they should go to Farmington, Connecticut, instead. That’s where Mrs. Basil E. Frankweiler lives—and Claudia is sure she can answer their questions about the statue.
Later, a taxi drops them off in front of Mrs. Basil E. Frankweiler’s sprawling mansion. At first the butler, Parks, won’t admit them, but when they explain they’re seeking answers about the Italian Renaissance, Parks finally leads them through antique-filled rooms and into Mrs. Frankweiler’s surprising office. It resembles a laboratory and is filled with rows of filing cabinets. Mrs. Frankweiler is a surprise, too—she’s an elderly lady wearing a lab coat and a baroque pearl necklace. When Mrs. Frankweiler finally turns around, she demands to know if they’re the children missing from Greenwich. The kids are flabbergasted. She shows them several newspapers reporting their disappearance but promises not to call the police if they won’t bore her with tedious questions.
Jamie finally stammers that they’re interested in Angel. Claudia says she can’t return home until she knows the truth about the sculpture’s origins. Mrs. Frankweiler says that’s her secret and asks where the Kincaids have been hiding for the past week. When Claudia says that’s their secret, Mrs. Frankweiler decides she likes these children.
At lunch, before Claudia emerges from a leisurely bath, Jamie confesses to Mrs. Frankweiler that they’d been hiding in the museum. Later, after Claudia joins them, Mrs. Frankweiler suggests that Claudia doesn’t want to go home because it turns out that running away didn’t change anything: she still had to do all the planning and supervising, just like at home. Claudia admits she’s right. She also says that Angel was her favorite part of running away, but she doesn’t want to explain why—if Mrs. Frankweiler knows their secret, it will feel like the whole adventure is over. Mrs. Frankweiler points out that everything ends eventually. Upset, Claudia realizes Jamie already spilled their secret.
Mrs. Frankweiler decides to help Claudia understand the value of their adventure—something that will help her grow up. She takes the children into her office and explains that the filing cabinets are filled with her “secrets.” One of the cabinets contains the secret of Angel. She gives them one hour to find the relevant file.
Claudia makes a list of categories related to Michelangelo and Angel, but after searching the cabinets for almost an hour, they haven’t located the proper files. The kids start squabbling, and when Jamie says, “Oh, boloney,” Claudia suddenly knows where to look. She looks for a folder labeled BOLOGNA—where Mrs. Frankweiler purchased the statue. Inside she finds a carefully preserved sketch of an angel, including Michelangelo’s mark. She bursts into tears.
Jamie wonders why Mrs. Frankweiler never sold the sketch. Mrs. Frankweiler explains that she’s always known Michelangelo sculpted Angel, but she kept the proof to herself—she needed the secret more than she needed the money. However, Mrs. Frankweiler will give the sketch to the Kincaids in her will, on one condition: they have to tell her their story. She knows Jamie will keep the secret because of the money at stake, and Claudia will keep the secret because it will make her feel “different”—“on the inside, where it counts.”
Claudia and Jamie agree to record their story for Mrs. Frankweiler. The next morning, Sheldon the chauffeur drives them home. On the way, the kids decide to “adopt” Mrs. Frankweiler as their grandmother and to secretly visit her every time they save up enough money.
Mrs. Frankweiler closes her written account for Saxonberg by insisting that Saxonberg take her to lunch at the Metropolitan’s restaurant; she’ll sign the revised will there. She hopes that Claudia and Jamie will visit her again and adds that she has another secret—that Saxonberg, her lawyer of 41 years, is the Kincaids’ grandfather.