In 1932, Mendès France was elected to the National Assembly as a deputy for the Eure département; he was the Assembly's youngest member. His ability was recognized at once, and, in the 1936 Popular Front government of Léon Blum, he was appointed Secretary of State for Finance. When World War II broke out, he joined the French Air Force. After the French surrender to Nazi Germany, he was arrested by the Vichy government authorities and sentenced to six years' imprisonment on a fallacious charge of desertion, but on 21 June 1941, he escaped and succeeded in reaching Britain, where he joined the Free French forces of Charles de Gaulle.
After serving with the Free French Air Force, Mendès France was sent by de Gaulle as his Finance Commissioner in Algeria, and then headed the French delegation to the 1944 monetary conference at Bretton Woods. When de Gaulle returned to liberated Paris in September 1944, he appointed Mendès France as Minister for National Economy in the provisional government.
But Mendès France soon fell out with the Finance Minister, René Pleven, when he favoured state regulation of wages and prices to control inflation (while Pleven favoured free market policies). When de Gaulle sided with Pleven, Mendès France resigned. Nonetheless, de Gaulle valued Mendès France's abilities, and appointed him as a director of the International Bank for Reconstruction and Development, and as French representative in the United Nations Economic and Social Council.
Mendès France immediately negotiated an armistice with Ho Chi Minh, the Vietnamese Communist leader. There was, he said, no choice but total withdrawal from Indochina, and the Assembly supported him by 471 votes to 14. Nevertheless, nationalist opinion was shocked, and Roman Catholic opinion opposed abandoning the Vietnamese believers to Communism. A tirade of abuse, much of it anti-Semitic, was directed at Mendès France. Jean-Marie Le Pen, then a Poujadist member of the Assembly, described his "patriotic, almost physical repulsion" for Mendès France.
Undeterred, Mendès France next came to an agreement with Habib Bourguiba, the nationalist leader in Tunisia, for the independence of that colony by 1956, and began discussions with the nationalist leaders in Morocco for a French withdrawal. He also favoured concessions to the nationalists in Algeria, but the fact that there were a million Pied-noirs there meant that there could be no easy way of out that situation. The future mercenary Bob Denard was convicted in 1954 to fourteen years of jail for an assassination attempt against him .
Mendès France hoped that the Radical Party would become the party of modernisation and renewal in French politics, by-passing the SFIO, a party mired in nostalgia for the 1930s. An advocate of greater European integration, he helped bring about the formation of the Western European Union, and proposed far-reaching economic reform. He also favoured defence co-operation with other European countries, but the National Assembly rejected the proposal for a European Defence Community, mainly because of misgivings about Germany's participation.
His cabinet fell in February 1955. In 1956 he served as Minister of State in the cabinet headed by the SFIO leader Guy Mollet, but resigned over the issue of Algeria, which was coming to dominate French politics. His split over Algeria with Edgar Faure, leader of the conservative wing of the Radical Party, led to Mendès France resigning as party leader in 1957.
Mendès France then joined the Unified Socialist Party (Parti Socialiste Unifié or PSU), a small party of the intellectual left. In 1967, he returned to the Assembly as a PSU member for the Isère, but again lost his seat in de Gaulle's 1968 landslide election victory. In accordance with the PSU, Mendès France expressed sympathy for the sentiments and actions of the student rioters during the "events" (les évènements) of May 1968, a position unusual for a politician of his age and status. In an unorthodox move, de Gaulle's socialist opponent, Gaston Defferre, had designated him Prime Minister-elect prior to the election; but to no avail for either. When Mitterrand formed a new Socialist Party in 1971, Mendès France supported him, but did not attempt another political come-back.
Shortly before Mendès France died in 1982, he witnessed the coming to office of Socialist President François Mitterrand.