The book follows siblings Claudia and Jamie Kincaid as they run away from home to the Metropolitan Museum of Art in New York City.

Early chapters depict Claudia and Jamie settling in at the Met: hiding in the restroom at closing time, as security staff check to see that all the patrons have departed; blending in with school groups on tour; bathing in the fountain; using "wishing coins" for money; and sleeping in Irwin Untermyer's antique bed.

A new exhibit draws sensational crowds and fascinates the children: the marble statue of an angel, the sculptor unknown but suspected to be Michelangelo.

When Konigsburg submitted Mixed-Up Files to Jean Karl at Atheneum in 1966, she was an unpublished mother of three children living in the suburbs of New York City.

[a] Konigsburg recalled years later that the Metropolitan Museum had purchased for only $225 a plaster and stucco statue from the time of the Italian Renaissance.

[9] The character of Mrs. Frankweiler was based on Headmistress Olga Pratt at Bartram's School for Girls in Jacksonville, Florida, where Konigsburg once taught chemistry.

"[9] On February 21, 2014, family and friends of E. L. Konigsburg gathered in a private space at the Metropolitan Museum of Art to pay tribute to the author, who died on April 19, 2013, at age 83.

By the time the children made their routine visits to the knights in armor, the mummy, and the Impressionists (at Laurie's request), Konigsburg's class would be finished and she would return to explore the museum with them.

And it was that moment, "burned into shrapnel memory", that he believes formed the kernel of the story that would become From the Mixed-Up Files of Mrs.

"[12] In a retrospective essay about the Newbery Medal-winning books from 1966 to 1975, children's author John Rowe Townsend wrote "Mrs. Frankweiler plays a vital part, and has an important affinity with Claudia; it is quite likely that she herself is a Claudia grown elderly...Yet the fact that Mrs. Frankweiler narrates the whole story, which she herself does not enter until near the end, seems to me to be a major structural flaw.

[14] Based on a 2007 online poll, the U.S. National Education Association listed it as one of its "Teachers' Top 100 Books for Children".