The book appeared on a 1964 list of "The Year's Best Juveniles" in The New York Times Book Review. One 1965 reviewer called the book "a brilliantly written, unsparing realistic story, a superb portrait of an extraordinary child". Another reviewer found that it "captures the feelings, thoughts and situations of a modern city child with remarkable clarity and dimension". Nevertheless, at least one reviewer in 1965 felt that the book dealt with "disagreeable people and situations". Although it was not chosen as one of the American Library Association (ALA) Notable Books for Children for 1964, years later it was included in a retrospective 1960–1964 ALA Notable Books List.
It won a Sequoyah Book Award in 1967. The paperback version was selected as one of the "Best in the Field" published during the previous 16 months in a 1968 New York Times article. In 1995, Paramount Pictures and Nickelodeon Movies claimed that 2.5 million copies of the book had been sold; however, the book did not appear on a 2001 Publishers Weekly list of "hardcovers that have sold 750,000 copies and paperbacks that have topped the one million copy mark."
Whitney Matheson wrote on the USA Today site in 2002 that Harriet "attracts dedicated, lifelong supporters". Anita Silvey in 2004 selected it as one of the 100 best books for children. In 2005, the ex-CIA officer Lindsay Moran cited the Harriet the Spy series of books as an inspiration for her career. It was included in a 2009 list of "Children’s Classics" by The Horn Book Magazine.
In a 2012 online poll of "Top 100 Children's Novels" by School Library Journal, the book ranked 17th. The book was 12th on a 2012 list of "The 50 Best Books for Kids" in Time Out New York Kids.
Despite its popularity, the book has been banned from some schools and libraries "because it was said to set a bad example for children". Along with Are You There God?, Blubber, and Where the Sidewalk Ends, the book was challenged at a 1983 school board meeting in Xenia, Ohio. Proponents of the Xenia ban stated that the book "teaches children to lie, spy, back-talk and curse", but the board voted to keep the books in the school libraries.
Although the book does not state the title character's sexuality, lesbians have identified with Harriet due to her being an "outsider" and due to her dressing like a boy. For example, Harriet wore high-top sneakers, a rarity for girls in the 1960s. Furthermore, Fitzhugh was known to be a lesbian, and the "Boy with the Purple Socks" character in the book may have been gay as the color purple is associated with the gay community. Harriet's friend Sport is also a departure from 1960s gender norms, as he cooks and cleans in addition to taking care of other household tasks due to his absentee mother and stay-at-home father who is consumed with trying to get his novel published.