Controversial pioneer in chemotherapy and other physical forms of treatment for mental disorders, he had a Methodist background. His paternal grandfather, a wealthy City merchant with an office in Mincing Lane, lived at Highgate. He died after a carriage accident and was succeeded in the business by William Sargant's father, Norman Thomas Carr Sargant, who was a fervent Methodist. His maternal grandfather was from Wales, who had given up his post as manager of a brewery after his conversion to become a preacher at Highgate. His mother belonged to the Walters family; five of his maternal uncles were preachers, two of whom became President of the WM Conference. His younger brother was Bishop Norman C. Sargant of the Church of South India.
Educated at The Leys School and St John's College, Cambridge, where he was a friend of Hugh Foot, he qualified as MRCS and LRCP in 1930 and in 1932 became medical superintendent at St Mary's Hospital, London. A period of depression left him deeply concerned about the care of mentally ill patients and he experimented with such physical treatments as lobotomy and electro-convulsive therapy at the Maudsley Hospital. He was visiting professor of Neuropsychiatry at Duke University Medical School, Durham NC, 1947-1948 and physician in charge of the Department of Psychological Medicine at St Thomas's Hospital, London, 1948-1972. He received the Starkey Memorial Prize of the Royal Society of Health in 1973.
He reacted against what he saw of the evangelical preaching for conversion in the southern States of America and in Battle for the Mind (1957) strongly criticized John Wesley's evangelistic methods as a form of brainwashing and indoctrination. He was answered at a theological level by M. Lloyd-Jones in Conversions Psychological and Spiritual (1959) and by Ian Ramage in Battle for the Free Mind (1967), a trenchant critique of both his philosophical assumptions and his treatment of historical data. His autobiography, published in 1967, was called The Unquiet Mind. He died on 27 August 1988.