Lewis was a close friend of J. R. R. Tolkien, and both authors were leading figures in the English faculty at Oxford University and in the informal Oxford literary group known as the "Inklings". According to his memoir Surprised by Joy, Lewis had been baptised in the Church of Ireland at birth, but fell away from his faith during his adolescence. Owing to the influence of Tolkien and other friends, at the age of 32 Lewis returned to Christianity, becoming "a very ordinary layman of the Church of England". His conversion had a profound effect on his work, and his wartime radio broadcasts on the subject of Christianity brought him wide acclaim.

In 1956, he married the American writer Joy Gresham, 17 years his junior, who died four years later of cancer at the age of 45.

Lewis died three years after his wife, as the result of renal failure. His death came one week before his 65th birthday. Media coverage of his death was minimal, as he died on 22 November 1963 – the same day that U.S. President John F. Kennedy was assassinated, and the same day another famous author died, Aldous Huxley.