In 1941, the year in which they graduated from the University of Oxford, Cornforth married Rita Harriet Harradence (b. 1915), with whom he had one son, John, and two daughters, Brenda and Philippa. Cornforth had met Harradence after she had broken a Claisen flask in their second year at the University of Sydney; Cornforth, with his expertise of glassblowing and the use of a blowpipe, mended the break. Rita Cornforth died on 6 November 2012, at home with her family around her, following a long illness.
On an important author or paper that was integral to his success, Cornforth stated that he was particularly impressed by the works of German chemist Hermann Emil Fischer.
Cornforth died in Sussex on 8 December 2013. at the age of 96. Cornforth is survived by his three children and four grandchildren. He was a sceptic and an atheist.