François Maspero's youth was marked by the engagement in the Resistance of his parents and the cultural environment of his family. His father, Henri Maspero, a sinologist and professor at the College de France, died at Buchenwald, but his mother managed to return alive from Ravensbruck. His grandfather, Gaston Maspero, who died before his birth, was an Egyptologist.
François Maspero opened a library in the Latin Quarter in 1955, aged 23. He created in 1959, in the middle of the Algerian War, the Maspero publishing house, along with Marie-Thérèse Maugis. They would be joined by Jean-Philippe Bernigaud and Fanchita Gonzalez Batlle, and then by Émile Copfermann. The first two collections, "Cahiers libres" and "Textes à l'appui", particularly focused on the Algerian War, from an anti-colonialist perspective, and contestation of the French Communist Party's stalinism. Maspero published Frantz Fanon's The Wretched of the Earth (1961), censored, with a preface from Jean-Paul Sartre, as well as L'An V de la Révolution algérienne. Maspero published others testimonies concerning Algeria, and the use of torture by the French Army, also censored. Beside being faced with courtsuits, Maspero was also the target of bombings.
He republished Paul Nizan, Les Chiens de garde and Aden Arabie, also with a preface from Sartre. Then, he created the review Partisans which survived until 1973. New-comers start in the Cahiers libres collection, such as Régis Debray in 1967 or Bernard-Henri Lévy in 1973. Georges Perec published his first texts in Partisans. In the 1960s, Maspero editions paid particular attention to the problems of the Third World and of neo-colonialism, publishing among others books by Che Guevara. He published Mongo Beti's 'Cruel hand on Cameroon, autopsy of a decolonization in 1972, which was censored by the Ministry of the Interior Raymond Marcellin on the request, brought forward by Jacques Foccart, of the Cameroon government, represented in Paris by the ambassador Ferdinand Oyono. In 1975, he republished Jean Maitron's classic History of the anarchist movement in France (1880–1914). In 1983, Maspero publishing house was transformed into the Éditions La Découverte, later bought by Vivendi Universal Publishing.
Maspero was criticized by Situationists such as Guy Debord, who used the term "masperize" to describe the falsification or corruption of a text, as by deleting segments from a quote without marking them.