[1] Its origins lie in Fritzi Ritz, a strip Bushmiller inherited from its creator Larry Whittington in 1925.

[2] The character of Nancy, a precocious eight-year-old, first appeared in the strip Fritzi Ritz, a comic about a professional actress and her family and friends.

"[5] Nancy became the focus of the daily strip, which was renamed for her in 1938 after Lawrence W. Hager, the editor of the Owensboro, Kentucky Inquirer-Messenger (now the Messenger-Inquirer), lobbied for the change;[5][6] Sluggo Smith, Nancy's friend from the "wrong side of the tracks" had been introduced earlier that year, and the strip's popularity rose.

Comics historian Don Markstein ascribed the strip's success to Bushmiller's "bold, clear art style, combined with his ability to construct a type of gag that appealed to a very broad audience.

In an interview in 2024, Scott said that he had never been an enthusiast of Nancy and only accepted the job as a way of breaking in to the newspaper strip industry, so after about a year he felt burnt out on imitating Bushmiller's style and wanted to try his own approach.

I'm excited to be sassy and grouchy through her voice instead of just mine" and "the Nancy I know and love is a total jerk and also gluttonous and also has big feelings and voraciously consumes her world".

Comics historian Tom Spurgeon described Jaimes as funny and talented, with an approach to the character that both breaks with and pays homage to Bushmiller's version.

[13][14][15] In the process, Jaimes updated the content of the strip, such as Nancy frequently using her smartphone and attending robotics classes.

The September 3, 2018, strip spawned an Internet meme, depicting Nancy riding a hoverboard using two phones, one of which was attached to a selfie stick, and proclaiming that "Sluggo is lit."

[19] The artists who followed Bushmiller drew in a range of styles that deviated distinctly from his deceptively simple approach.

Bushmiller refined and simplified his drawing style over the years to create a uniquely stylized comic world.

The American Heritage Dictionary of the English Language illustrates its entry on comic strip with a Nancy cartoon.

Despite the small size of the reproduction, both the art and the gag are clear, and an eye-tracking survey once determined that Nancy was so conspicuous that it was the first strip most people viewed on a newspaper comics page.

Walls, floors, rocks, trees, ice-cream cones, motion lines, midgets and principals are carefully positioned with no need for further embellishment.

Nancy also had its own monthly comic book magazine of newspaper reprints in Norway (where the strip is known as Trulte) during 1956–1959.

[80] A third cartoon, Nancy's Little Theatre, was announced with a release date of October 16, 1942,[81] but seems not to have been completed; Motion Picture Herald was the only trade journal to include it in booking listings, and later pulled it.

Nancy appeared along with seven other comic strip characters: Emmy Lou, Broom-Hilda, Dick Tracy, The Dropouts, Moon Mullins, the Captain and the Kids and Smokey Stover.

Nancy also appeared on the back cover of the popular Arabic children magazine Majid during the 80s, she was known as Moza while Sluggo was portrayed as her brother Rashoud.

On October 1, 2019, Andrew McMeel Publishing released a spin-off board book, Nancy's Genius Plan, written and illustrated by Jaimes.