Radiguet was born in Saint-Maur, Val-de-Marne close to Paris, the son of a caricaturist. In 1917 he moved to the city. Soon he would drop out of the Lycée Charlemagne, where he studied, in order to pursue his interests in journalism and literature. He associated himself with the Modernist set, befriending Picasso, Max Jacob, Jean Hugo, Juan Gris and especially Jean Cocteau, who became his mentor. Radiguet also had several well-documented relationships with women. An anecdote told by Ernest Hemingway has an enraged Cocteau charging Radiguet (known in the Parisian literary circles as "Monsieur Bébé" — Mister Baby) with decadence for his tryst with a model: "Bébé est vicieuse. Il aime les femmes." ("Baby is depraved. He likes women." [Note the use of the feminine adjective]). Radiguet, Hemingway implies, employed his sexuality to advance his career, being a writer "who knew how to make his career not only with his pen but with his pencil."

In early 1923 Radiguet published his first and most famous novel, Le Diable au corps (The Devil in the Flesh). The story of a young married woman who has an affair with a sixteen-year-old boy while her husband is away fighting at the front provoked scandal in a country that had just been through World War I. Though Radiguet denied it, it was established later that the story was in large part autobiographical. Critics, who initially despised the intense publicity campaign for the book's release (something not normally associated with works of literary merit at the time), were finally won over by the quality of Radiguet's writing and his sober, objective style.

His second novel, Le bal du Comte d'Orgel, also dealing with adultery, was only published posthumously in 1924.

Radiguet died in 1923 at age 20 of typhoid fever, which he contracted after a trip he took with Cocteau. In reaction to this death Francis Poulenc wrote, "For two days I was unable to do anything, I was so stunned". Alongside these two novels, Radiguet's works include a few poetry volumes and a play.

In 1947 Claude Autant-Lara released his film Le diable au corps, based on Radiguet's novel, and starring Gérard Philipe. Coming just after World War II, the movie caused controversy in its turn. Among the other cinematic versions of Radiguet's story, the heavily adapted version by Marco Bellocchio, Il diavolo in corpo (1986), was notable as being among the first mainstream films to show unsimulated sex.

Steadman and Blake (1945) write that admirers of his first novel "include the most discriminating of critics." Aldous Huxley is quoted as declaring that Radiguet had attained the literary control that others required a long career to reach. François Mauriac said that Le Diable au corps is "unretouched and seems shocking, but nothing so resembles cynicism as clairvoyance. No adolescent before Radiguet has delivered to us the secret of that age: we have all falsified it."