Léon Werth was born in Remiremont, in the mountainous Vosges region of eastern France, to an assimilated Jewish family. His maternal uncle was the philosopher Frédéric Rauh.
He was a prize-winning student at the Lycée Henri-IV in Paris, but abandoned his studies to become an art critic and columnist for various magazines. His first important novel, La Maison blanche, was a finalist for the Prix Goncourt in 1913. In World War I, he served more than a year in the French army as a radio operator before receiving a medical discharge for a lung infection. His anti-war novel Clavel, soldat, which caused a scandal when it was published in 1919, was later cited as among the more realistic depictions of trench warfare. In the 1920s and 30s, he wrote books and articles criticizing the French colonial empire, the Soviet Union, and the growing Nazi movement.
He became a close friend of Antoine de Saint-Exupéry, who dedicated Le Petit Prince (The Little Prince) to Werth. After the German invasion of France in World War II, Werth and his wife Suzanne fled the Nazis to Saint-Amour, a village in the Jura Mountains. There he wrote an eyewitness account and memoir of this tumultuous experience before giving the manuscript to Saint-Exupéry, who smuggled it out of France via Algeria and Portugal. It was then lost for 50 years, and Werth never saw it published. It first appeared in France in 1992, and the first English edition, called simply 33 Days, appeared in 2015. Werth survived the war and became a contributor to the intellectual magazine Liberté de l'Esprit run by Claude Mauriac.