Charles E. Piers studied at the South African College, Cape Town, from 1865 to 1868. In the latter year he was awarded the third-class Certificate in Literature and Science (equivalent to matriculation) by the Board of Public Examiners of the Cape of Good Hope. He then proceeded to Ireland, where he studied medicine at Trinity College, Dublin, and Meath Hospital, and qualified as a member of the Royal College of Surgeons of England (MRCS) in 1872 and as a licentiate of the King's and Queen's (later Royal) College of Physicians of Ireland in 1873. In May 1873 he was licensed to practice in the Cape Colony. He subsequently studied at the Universities of Edinburgh and Aberdeen and was awarded the degrees Bachelor of Medicine (BM, 1880), Master of Surgery (CM) and Doctor of Medicine (MD), the last two by the University of Aberdeen, both in 1896.
In 1884 Piers resided in King William's Town, where he served on the first committee of management of the King William's Town Naturalist's Society. He was still there in January 1886, when he served (with Dr H.M. Chute*, Dr C.J. Egan* and Mr J.D. Ellis*) on a committee of the society which reported on insect pests. During these years he held the positions of acting district surgeon of King William's Town, and acting surgeon at Grey Hospital. However, by 1893 he had settled in Cape Town, where he was still practising in 1907. He served as medical officer of St George's Orphanage and was a member of the Cape of Good Hope Branch of the British Medical Association. Between 1887 and 1895 he contributed several articles to the first and second series of the South African Medical Journal, on how typhoid fever is spread (1887), diphtheria and its treatment (1888, 1889, 1895), and a peculiar case of spinal meningitis (1889).
Dr Piers collected various zoological specimens which he presented to the South African Museum, Cape Town, in 1898. These included the skull of an African killed at the Fish River, ten skulls of South African mammals, 23 snakes, 18 lizards, some scorpions and two molluscs. He also donated a Basuto ivory armband and a "Bushman whorl stone".