Fitzhugh is best known for her 1964 novel Harriet the Spy, a fiction work about an adolescent girl's predisposition with a journal covering the foibles of her friends, her classmates, and the strangers she is captivated by.

[3] He graduated from Emory University and met Louise Perkins, an aspiring tap dancer, in 1926 on a boat traveling from New York to England.

[3][4] They married, but his family disapproved of the marriage due to her lower social standing and they divorced after a year, shortly following Fitzhugh's birth in 1928.

[3] When Fitzhugh was a teenager, she discovered the truth while working at the Memphis newspaper, The Commercial Appeal and finding coverage of the divorce proceedings in the archive.

[2] She graduated in 1946[3] from Miss Hutchison's School where she had been popular, but felt out of place as a debutante in upper-class society, and was appalled by her peers' racist attitudes.

Although a parody of both Eloise and beatnik conceit, the book sprang to life as a genuine work of literature and was immediately popular with both adults and children.

[2] Fitzhugh continued to be a successful painter in New York, showing her work, primarily realistic portraits, nudes, and city scenes, alongside artists like Jacob Lawrence, Ad Reinhardt, and Louise Nevelson.

A curious and solitary child, she spends her time spying on other people, often her friends and neighbors, recording her cynical and bluntly rude observations in a notebook.

In 2010, it was adapted as the Disney movie, Harriet the Spy: Blog Wars and in 2021 as an animated series by Apple TV+ starring Beanie Feldstein.

[13] Fitzhugh was romantically linked to actress Constance Ford, casting director Alixe Gordin, and her Suzuki Beane collaborator, Sandra Scoppettone.