John Cornwell was born in London, the son of Sidney Arthur Cornwell and Kathleen Egan Cornwell.
Cornwell entered the junior seminary, Cotton College, in 1953 as a candidate for the priesthood, and proceeded to the senior seminary Oscott College, Sutton Coldfield, in 1958.
After leaving the seminary, in the 1960s Cornwell studied at Oxford and Cambridge, graduating in 1964 in English Language and Literature. After studying at Christ's College, Cambridge, as a graduate student, he taught in London schools, and at McMaster University, Ontario. His first two books were novels: The Spoiled Priest, and Seven Other Demons.
In 1973 he published a critical biography of Samuel Taylor Coleridge, ''Coleridge, poet and revolutionary (1772–1804).
His 1989 book A Thief in the Night investigates the 1978 death of Pope John Paul I, which was surrounded by conspiracy theories. Though Cornwell sharply criticized Vatican prelates, he concluded that the Pope was not murdered but died of a pulmonary embolism, possibly brought on by overwork and neglect.
In 1999, Cornwell published Hitler's Pope, in which he accuses Pope Pius XII of assisting in the legitimization of the Nazi regime in Germany through the pursuit of a Reichskonkordat in 1933 and of remaining silent during the Holocaust.
Five years after the publication of Hitler's Pope, Cornwell had somewhat modified his views: "I would now argue, in the light of the debates and evidence following Hitler's Pope, that Pius XII had so little scope of action that it is impossible to judge the motives for his silence during the war, while Rome was under the heel of Mussolini and later occupied by Germany.
In 2004, Cornwell followed up Hitler's Pope with Hitler's Scientists.
In the same year, Cornwell published A Pontiff in Winter, a work highly critical of Pope John Paul II. The book has been criticized as "a hatchet job
In 2006, he published his autobiography, titled Seminary Boy.
Cornwell is also Director of the Science and Human Dimension Project at Jesus College, Cambridge. In this capacity he criticized "reductionist brain science" for "its failure even to mention, let alone give an account of, human imagination".
In 2006 and 2007, he criticized Richard Dawkins and his book The God Delusion for its extremist tone as well as for lapses in logic, imagination and understanding. Cornwell followed up these articles with his book Darwin's Angel, published in 2007.