Born in Castres, Tarn to a wealthy family, Peyrefitte went to Jesuit and Lazarist boarding schools and then studied language and literature in Toulouse. After graduating first of his year from Institut d'Études Politiques de Paris in 1930, he worked as an embassy secretary in Athens between 1933 and 1938. Back in Paris, he had to resign in 1940 for personal reasons before being reintegrated in 1943 and finally ending his diplomatic career in 1945. In his novels, he often treated controversial themes and his work put him at odds with the Roman Catholic church.

He wrote openly about his homoerotic experiences in boarding school in his 1944 first novel Les amitiés particulières (Particular Friendships -- a term used in seminaries to refer to friendships seen as too close and exclusive, often incorrectly translated as "Special Friendships"), which won the coveted prix Renaudot in 1945. The book was made into a film of the same name which was released in 1964. On the set, Peyrefitte met the 12 year old Alain-Philippe Malagnac d'Argens de Villèle; Peyrefitte tells the story of their relationship in Notre amour ("Our Love" - 1967) and L'Enfant de cœur ("Child of the Heart" - 1978). Malagnac later married performer Amanda Lear.

A cultivator of scandal, Peyrefitte attacked the Vatican and Pope Pius XII in his book Les Clés de saint Pierre (1953), which earned him the nickname of 'Pope of the Homosexuals'. The publication of the book started a bitter quarrel with François Mauriac. Mauriac threatened to resign from the paper he was working with at the time, L'Express if it did not stop carrying advertisements for the book. The quarrel was exacerbated by the release of the film adaptation of Les amitiés particulières and culminated in a virulent open letter by Peyrefitte in which he accused Mauriac of homophile inclinations and called him a tartuffe. In April 1976, after Pope Paul VI had condemned homosexuality in a homily, Peyrefitte accused him of being a closet homosexual.

In Les Ambassades (1951), he revealed the ins and outs of diplomacy. Peyrefitte also wrote a book full of gossip about Baron Jacques d'Adelswärd-Fersen's exile in Capri (L'Exilé de Capri, 1959) and translated Greek gay love poetry (La Muse garçonnière (The Boyish Muse), Flammarion, 1973).

In his memoirs Propos Secrets, he wrote extensively about his youth, his sex life (homosexual mainly and a few affairs with women), his years as a diplomat, his travels to Greece and Italy and his troubles with the police for sexually harassing male teenagers. He also gave vent to his fierce love of snobbish genealogizing and vitriolic well-documented gossip, writing about famous people of his time such as André Gide, Henry de Montherlant, Jean Cocteau, Jean Genet, Marcel Jouhandeau, Marie-Laure de Noailles, Gaston Gallimard, Jean Paul Sartre, Charles de Gaulle and Georges Pompidou, among many others. Claiming he had reliable sources within the Vatican's "black aristocracy", once again he stated that three recent popes of the 20th century were homosexuals. He particularly loved to expose the hypocrisy and vanity of prominent people, to denounce fake aristocrats and to out closet homosexuals.

Roger Peyrefitte wrote popular historical biographies about Alexander the Great and Voltaire. In Voltaire et Frédéric II he polemically claimed that Voltaire had been the passive lover of Frederick the Great.

In spite of his libertarian views on sexuality, politically Peyrefitte was a conservative bourgeois and in his later years he would support extreme right-winger Jean-Marie Le Pen.

He died at 93 of Parkinson's disease, after receiving the last rites from the Church he had attacked so strongly.