Cyril Clarke was born on 22 August 1907 in Leicester, England and received his school education at Wyggeston Grammar School for Boys, Leicester and at the independent Oundle School near Peterborough. His interest in butterflies and moths began at school. His studied natural science at Gonville and Caius College, Cambridge, graduating in 1929, and then Medicine at Guy's Hospital, London, graduating in 1932. During the Second World War he worked as a medical specialist in the Royal Naval Volunteer Reserve. After the war Clarke worked as a registrar at the Queen Elizabeth Hospital in Birmingham and then as Consultant Physician at the United Liverpool Hospitals. In 1963 he was appointed Director of the Nuffield Unit of Medical Genetics based at the University of Liverpool and two years later was made Professor of Medicine. He held these posts until his retirement in 1972. In retirement he served as President of the Royal College of Physicians (1972–1977)
He married Frieda (or Féo) in 1934. Lady Clarke died in 1998. Cyril Clarke died in 2000. They had three sons, one of whom is a consultant Neurologist.
Clarke answered an advert in an insect magazine for swallowtail butterfly pupae that had been placed by Philip Sheppard. They met and began working together in their Common interest of lepidoptery. From 1959 they started running a moth trap in Caldy Common near West Kirby, Wirral, England. They studied the peppered moth, the scarlet tiger moth and swallowtail butterfly. They published papers on the genetics of Lepidoptera and also on Rh disease. Clarke continued research in his retirement and in 1988 he rediscovered a scarlet tiger moth colony on the Wirral Way, West Kirby, that had been started in 1961 by Philip Sheppard. The colony was useful for study of the genetics of changes in populations.