After the death of his mother in 1906, when he was two years old, Cecil was brought up in London by his father, with the help of an aunt, spending summer holidays with relatives in County Wexford. He was educated at Sherborne School and at Wadham College, Oxford. In Oxford, Day-Lewis became part of the circle gathered around W. H. Auden and helped him to edit Oxford Poetry 1927. His first collection of poems, Beechen Vigil, appeared in 1925.

In 1928 Day-Lewis married Constance Mary King, the daughter of a Sherborne master (i.e. teacher). Day-Lewis worked as a schoolmaster in three schools, including Larchfield School, Helensburgh, Scotland (now Lomond School). During the 1940s he had a long and troubled love affair with the Novelist Rosamond Lehmann. His first marriage was dissolved in 1951, and he married Actress Jill Balcon, daughter of Michael Balcon.

After the late 1930s, which were marked by the widespread purges, repression, and executions under Josef Stalin in the Soviet Union, Day-Lewis gradually became disillusioned with communism. In his autobiography, The Buried Day (1960), he renounces former communist views. His detective novel, The Sad Variety (1964), contains a scathing portrayal of doctrinaire communists, the Soviet Union's repression of the 1956 Hungarian uprising, and the ruthless tactics of Soviet intelligence agents.

In his youth and during the disruption and suffering of the Great Depression, Day-Lewis adopted communist views, becoming a member of the Communist Party of Great Britain from 1935 to 1938. His early poetry was marked by didacticism and a preoccupation with social themes. In 1937 he edited The Mind in Chains: Socialism and the Cultural Revolution. In the introduction, he supported a popular front against a "Capitalism that has no further use for culture". He explains that the title refers to Prometheus bound by his chains, quotes Shelley's preface to Prometheus Unbound and says the contributors believe that "the Promethean fire of enlightenment, which should be given for the benefit of mankind at large, is being used at present to stoke up the furnaces of private profit". The contributors were: Rex Warner, Edward Upward, Arthur Calder-Marshall, Barbara Nixon, Anthony Blunt, Alan Bush, Charles Madge, Alistair Brown, J. D. Bernal, T. A. Jackson and Edgell Rickword.

Day-Lewis was born in 1904 in Ballintubbert, Athy/Stradbally border, Queen's County (now known as County Laois), Ireland. He was the son of Frank Day-Lewis (died 29 July 1937), Church of Ireland Rector of that parish, and Kathleen Blake (née Squires; died 1906). Some of his family were from England (Hertfordshire and Canterbury). His father took the surname "Day-Lewis" as a combination of his own birth father's ("Day") and adoptive father's ("Lewis") Surnames. In his autobiography The Buried Day (1960), Day-Lewis wrote, "As a Writer I do not use the hyphen in my surname – a piece of inverted snobbery which has produced rather mixed results".

During the Second World War he worked as a publications Editor in the Ministry of Information, an institution satirised by George Orwell in his dystopian Nineteen Eighty-Four, but equally based on Orwell's experience of the BBC. During the Second World War his work was now no longer so influenced by Auden and he was developing a more traditional style of lyricism. Some critics believe that he reached his full stature as a poet in Word Over All (1943), when he finally distanced himself from Auden. After the war he joined the publisher Chatto & Windus as a Director and senior Editor.

In 1946, Day-Lewis was a lecturer at Cambridge University, publishing his lectures in The Poetic Image (1947). Day-Lewis was made a Commander of the Most Excellent Order of the British Empire by Elizabeth II in her 1950 Birthday Honours. He later taught poetry at Oxford, where he was Professor of Poetry from 1951 to 1956. During 1962–1963, he was the Norton Professor at Harvard University. Day-Lewis was appointed Poet Laureate in 1968, in succession to John Masefield.

Cecil Day-Lewis died from pancreatic cancer on 22 May 1972, aged 68, at Lemmons, the Hertfordshire home of Kingsley Amis and Elizabeth Jane Howard, where he and his family were staying. As a great admirer of Thomas Hardy, he arranged to be buried near the author's grave at St Michael's Church in Stinsford, Dorset.

Day-Lewis fathered four children . His first two children, with Constance Mary King, were Sean Day-Lewis, a TV critic and Writer, and Nicholas Day-Lewis, who became an Engineer. His children with Balcon were Tamasin Day-Lewis, a television chef and food critic, and Daniel Day-Lewis, who became an award-winning actor . Sean Day-Lewis published a biography of his father, C. Day Lewis: An English Literary Life (1980).

Daniel Day-Lewis donated his father’s archive to the Bodleian library.