Stafford Cripps was born in 1889 in London to Charles Alfred Cripps and his wife Theresa. His father was a Conservative MP and later a Labour cabinet minister.

After turning down a scholarship to New College, Oxford, in 1907 he studied for an MSc degree at University College, London. In 1911, he married Isobel Cripps (née Swithinbank), whom he had met a year earlier when helping out with his father's campaign. When war broke out in 1914, Cripps, still recovering from a breakdown, did not join the forces. Instead, he became a lorry driver for the Red Cross. In 1929, Cripps joined the Labour Party and became a minister in Ramsay MacDonald's Labour government the year after. His campaign to become an MP was supported by Sukhsagar Datta. In 1933 he became chairman of the Socialist League, which he dissolved in 1937. Cripps was also heavily involved with the Left Book Club.

At the outbreak of the Second World War in 1939, Cripps went on a tour of India, China, Russia and the United States. Cripps' first visit to India was intended to explore the possibility of self-government; he was warmly received by Jawaharlal Nehru. After India he went to China where he befriended Chiang Kai-shek, then he went to Russia where he met Foreign Minister Molotov. From June 1940 to January 1942 he served as the British Ambassador to the Soviet Union. Cripps succeeded in bringing Russia and Britain together as allies during the war, and consequently, in February 1942, Churchill brought Cripps into the government as Lord Privy Seal and Leader of the House of Commons. Only a month later, on 22 March, Cripps would fly to Delhi on the so-called Cripps Mission, which was intended to secure Indian self-government after the war in return for support in the British war effort. The Cripps Mission failed and the Indian National Congress and the British Government became further estranged. The failure of the mission was the catalyst for Gandhi  to launch the Quit India movement in August 1942. After his return to Britain, Cripps' status within the Government had diminished and in the autumn of that year he resigned from the War Cabinet and took up the post of Minister of Aircraft Production.

After Clement Attlee's Labour victory in 1945, Cripps remained interested in the question of Indian independence, and from March to June 1946 Cripps travelled to India for the third time, along with Secretary of State, Lord Pethick-Lawrence, and Lord of the Admiralty, A. V. Alexander. The Cabinet Mission's offer of a three-tier structure was accepted by Jinnah and the Muslim League but Gandhi and the Congress turned it down. Cripps realized that the future government of India lay in the hands of the Indian leaders. By the end of 1946, at the behest of Cripps, Attlee appointed Lord Mountbatten the last Viceroy of India and set a date for British withdrawal. This paved the way to Independence and Partition in 1947.

In 1947, Cripps was appointed Minister for Economic Affairs but took over the post of Chancellor of Exchequer six weeks later. He fought hard to restore the British economy in the post-war years. At this point, Cripps was also seriously ill and was reconvalescing at the Bircher Benner clinic in Zürich. Cripps resigned as Chancellor and as MP on 20 October 1950 on grounds of ill health. He died at the Bircher Benner Clinic on 21 April 1952.