Born in Castres, in the southwestern department of Tarnes, France, his family were prosperous landowners. He was educated at the Lazarist Collège St Benoit. He then attended the Jesuit Collège de Caousou at Audouane, followed by the Collège de Caousou at Toulouse, and the Lycée de Foix and the Faculty of Letters at the University of Toulouse where he majored in language and literature. He then went to Paris and acquired the diploma of Ecole Libre des Sciences Politiques in the diplomatic section.

His career in diplomacy began at the Ministre des Affaires Etrangères in 1931. In 1933 he became the first secretary at Athens, and in 1938 he entered the administration centrale and was attached to the Ministre des Affaires Etrangères in Paris. He then returned to Paris, and in 1940 resigned after a near-scandal involving an adolescent boy.

In 1943 he became assistant to Ferdinand de Briton, the representative of the government to the German occupying authorities. He was removed from office in February 1945 because of his collaboration. The discharge was revoked in 1960 and his diplomatic status was restored in 1962.

He became famous with his first novel, Les Amitiés particulières in 1944. The story deals with gay love affairs at a French boarding school, and appears to draw on Roger Peyrefitte's own experiences. He never had the same degree of success with his other novels.

Some continued the theme of gay love affairs. In 1964 a literary dispute developed between Roger Peyrefitte and Françoise Mauriac over the making of a film of Les Amitiés particulières. The argument split the Paris literary world and led to many resignations from the Société des Gens de Lettres.

His Les Clefs de Saint-Pierre, (1955) was described as "lewdly libellous" by the Vatican. In 1958 the Italian government began criminal proceedings against him on the grounds that he libelled Pope Pius IX in an article in a Rome newspaper. In 1965 a judge ordered a page to be cut from Les Juifs after the Rothschild family took legal action. Les Américains, (1968), portrayed Marlene Dietrich as a supporter of Hitler and led to her winning libel damages against Roger Peyrefitte. His Propos Secrets, (1977) involved him in a series of libel actions. He also wrote historical novels including L'Exilé de Capri, about Baron Jacques d'Adelsward Fersen in Capri.

The love of his life appears to have been Alain-Philippe Malagnac d'Argens de Villele, the schoolboy who played the role of one of the choorboys in the 1964 film Les Amitiés particulières. Their relationship gave rise to another novel, Notre Amour (1967), which itself became a subject od scandal. At the age 16, having completed his baccalauréat, Malagnac became Peyrefitte's secretary. They also travelled together, following in the footsteps of Alexander the Great. Peyrefitte adopted Malagnac and in 1979, had him married with Amanda Lear. Malagnac died in 2000, aged 51, in a fire of their house, while in company with a 20-year-old man.

In November 1992 he was made to look foolish when invited onto the French television book programme, Ex Libris, to defend his two-volume biography Voltaire et Fredédéric II in which Fredédéric II sodomised Voltaire. The whole story was treated as preposterous, but the book became a best-seller.

Peyrefitte died in Paris.