Sir John Burton Cleland was born at Norwood, South Australia, on 22 June 1878, the son of Dr WL Cleland, the former Colonial Surgeon for South Australia. He was educated at Prince Alfred College and commenced studying medicine at the University of Adelaide in 1895. Cleland completed his medical studies at the University of Sydney where he attained an MB and ChM in 1900 and a Doctorate of Medicine in 1902. In 1903 he travelled to the United Kingdom where he completed further medical studies in pathology, bacteriology and tropical medicine and was appointed the Cancer Research Scholar, London Hospital from 1904-05. When he returned to Australia, Cleland was appointed Western Australia's Government Pathologist and Bacteriologist in 1906, a position he held until 1909. He then moved to New South Wales (NSW) where he was appointed Principal Microbiologist in the New South Wales Department of Public Health. Cleland remained in that position until 1919. In the following year he was appointed the Marks Professor of Pathology at the University of Adelaide, a position he retained until his retirement in 1948. For many years he was honorary consulting pathologist at the Royal Adelaide Hospital and the Adelaide Children's Hospital, and was a member of the Central Board of Health for South Australia from 1936 to 1965.

Cleland married Dora Paton in 1908 and they had one son and four daughters. He died in Adelaide on 11 August 1971, aged 93.

Sir John Cleland maintained a strong interest in the study of Australian Aboriginal anthropology. He was a member and Chairman of the South Australian Advisory Council on Aborigines from 1932-36, Chairman of the Aborigines Protection Board (APB) from 1940-62 and a member of the Aboriginal Affairs Board from 1962-65. As a member of the APB he travelled widely throughout South Australia, visiting Aboriginal people on the various reserves and missions as well as pastoral stations and country towns.

Cleland was one of the founding members of the Board for Anthropological Research (BAR) at the University of Adelaide and the Chairman of the Board from 1930-65. He participated in many of the BAR expeditions to central Australia, including Hermannsburg (1929), MacDonald Downs (1930), Cockatoo Creek (1931), Mt Liebig (1932), Ernabella (1933), Ooldea (1934), Diamantina (1934) and the Granites (1936). He was an Honorary Associate of the South Australian Museum (SAM) for many years and a foundation and long-standing member of the Anthropological Society of South Australia. He was elected President of the Society in 1930, 1946 and 1958. His principal interests in relation to the Aboriginal people were diseases and health issues, but he was also interested in ecology and Aboriginal use of flora and fauna. Cleland published numerous papers in anthropology, some of which are listed below.

As well as anthropology, Cleland's lifelong interests were ornithology, botany, natural history and conservation. He joined the Royal Australian Ornithological Union in 1902 and served as President in 1935-36, and was made an Honorary Member in 1949 in recognition of his contribution to ornithology. He was also a member of the SA Ornithological Association from 1920 until his death and served as President at various times between the 1920s and 1940s. He contributed numerous papers to ornithological journals such as Emu and the South Australian Ornithologist. His collection of over 400 bird skins was presented to SAM in 1956.

In 1934-35 Cleland published two volumes on South Australian fungi which continue to be used as textbooks and major reference works and he also published many other papers on fungi and vascular plants. During his anthropological travels, he collected up to 30,000 plant specimens which he later donated to the South Australian Herbarium and other interstate herbariums.

Cleland joined the Royal Society of South Australia in 1895 and served on the Council in the 1920s and 1930s. He was elected Vice-President in 1926-27 and served as President in 1927-28 and 1941-42.

Cleland was appointed a Commissioner of the National Park (Belair) in 1926, became Deputy Chairman in 1931 and was appointed Chairman of Commissioners in 1936. With the establishment of the National Trust and amendments to the National Parks Act in 1955, he became Chairman of the Commissioners of the National Park and Wildlife Reserves, a position he held until 1965, and he was Deputy Chairman from 1965 to 1969. He also served on the Fauna and Flora Board which administered Flinders Chase on Kangaroo Island and the Flora and Fauna Advisory Committee, which advised the Minister of Agriculture. Cleland was a member of the Field Naturalists' Society of SA from 1892 until his death. The Cleland Conservation Park in the Mount Lofty Ranges was named after him.

Cleland was awarded many medals and distinctions during his career, including the Verco Medal from the Royal Society of South Australia in 1933, the Lord Medal from the Royal Society of Tasmania in 1939 and the Australian Natural History Medallion in 1952. In 1964 he was awarded the John Lewis Medal by the Royal Geographical Society of Australasia (SA Branch). He was awarded the order of Commander of the British Empire in 1949 for his services to medicine and he was knighted in 1964.

The Mortlock Library of South Australiana has an extensive collection of Cleland's diaries, manuscripts, notes, correspondence and photographs. The Barr-Smith Library at the University of Adelaide also has an extensive collection of Cleland's correspondence, notebooks, reports, papers and other documentary material.