Sydney Skaife was born in London, England on 12 December 1889 and grew up in Bath, Somerset. He initially studied Arts at Reading University, although his real passion was Biology. In 1911 he received his Teaching Diploma and in 1912 he went to the University of Leipzig in Germany.
In 1913 he came to Cape Town to teach Biology at Ronderbosch Boys High School, after which he accepted a post as entomologist at the Rosebank Research Station in Cape Town. Here he worked on insects that fed on stored grain which was a particularly urgent issue at the time, since large quantities of grain were being stored at the Cape as part of the war effort.
On 29 September 1917 he married Elsie Mary Croft and they had two children together. Shortly after his marriage, he was transferred to the Cedara College of Agriculture in Natal where he worked on bees and wattle bagworm infestation.
In 1920 he received an M.Sc. at the Natal University College and in 1922 he received a Ph.D from the University of Cape Town for his research on bean weevils. From 1921 to 1945 he was the Inspector of Science in the Cape Department of Education.
In 1929 he established the Wild Life Protection and Conservation Society, now called the Wildlife Society of Southern Africa. In his capacity as chairman, he helped to establish the Outeniqua Mountain Zebra Reserve, the Bontebok Park, and the Addo Elephant Reserve.
In 1939, largely through his efforts, the Cape of Good Hope Nature Reserve was established. He became President of the Entomological Society of Southern Africa in 1940, and also served as Chairman of the newly created Fisheries Development Corporation from 1945-1951. During the same period he was also a member of the Board of Governors of the South African Broadcasting Corporation.
In 1952 he retired to his home in Hout Bay and did extensive research on the social behaviour of ants, bees and wasps which resulted in the publication of several books and scientific publications. At this time he was also awarded the South African Medal and Grant for scientific research by the South African Association for the Advancement of Science.
In 1957 he was awarded a D.Sc. by the University of Natal and, despite being retired, became the President of the Zoological Society of South Africa in 1960.
He died on 6 November 1976 at his home in Hout Bay.