The strip features a six-year-old girl named Mafalda, who reflects the Argentine middle class and progressive youth, is concerned about humanity and world peace, and has an innocent but serious attitude toward problems.

[4] He had received a proposal by fellow artist Miguel Brascó, and the comic strip would be a covert advertisement for the "Mansfield" line of products of the Siam Di Tella company.

Quino and Brascó offered the comic strip to the newspaper Clarín, but they noticed the advertisement nature and did not publish it.

The covert advertising campaign was never carried out, but Brascó published portions of those comics at the magazine Leoplán.

Julián Delgado, senior editor of the magazine Primera Plana, proposed Quino to publish the comic strip, if he removed the advertisements.

After creating the characters of Mafalda's little brother Guille and her new friend Libertad, he definitively ceased publication of the strip on 25 June 1973.

[13] In the United States of America, his only published work is The World of Quino (1986); an English version of Mafalda for the Anglophone market, translated by Frank Wynne, is scheduled to be released in 2025 by Elsewhere Editions.

In 1993 Cuban filmmaker Juan Padrón, a close friend of Quino, directed 104 short animated Mafalda films, backed by Spanish producers.

[18] Mafalda has occasionally been pointed out as being influenced by Charles Schulz's Peanuts, most notably by Umberto Eco, in 1968, who contrasted the two characters.

"[20] In 2009, a life-sized statue of Mafalda was installed in front of Quino's old home in the San Telmo neighborhood of Buenos Aires.

[22] In 2014, a life-sized statue of Mafalda was installed in Campo de San Francisco, a park located in Oviedo, Principality of Asturias' capital (northern Spain), after the Princess of Asturias Awards was conferred to Quino, for the creation of Mafalda, in the category of Communications and Humanities.