Educated in California, he did his first fieldwork in the Solomon Islands during World War II before returning to the USA. He became director of the ornithological laboratory at Cornell and then the Peabody Museum at Yale.
Sibley developed an interest in hybridisation and its implications for evolution and taxonomy and, in the early 1960s he began to focus on molecular studies: of blood proteins, and then the electrophoresis of egg-white proteins.
By the early 1970s Sibley was pioneering DNA-DNA hybridisation studies, with the aim of discovering, once and for all, the true relationships between the modern orders of birds. These were highly controversial to begin with, and regarded by colleagues as anything from pure snake-oil salesmanship on the one hand to Holy Writ on the other. With the passage of time and ever-improving laboratory methods, the balance of scientific opinion has shifted closer to the latter interpretation, though the picture is by no means clear-cut and simple.
During the 1970s, Sibley was a highly controversial figure in ornithological circles, for both professional and personal reasons. His friend Richard Schodde, writing Sibley's obituary in Emu, commented that he was:
In 1990 Sibley was elected President of the International Ornithological Congress. His landmark publications, Phylogeny and Classification of Birds (written with Jon Ahlquist) and Distribution and Taxonomy of Birds of the World (with Burt Monroe) are among the most-cited of all ornithological works.
Sibley's sequence has been taken up largely unchanged by the American Ornithologists' Union, and although the equivalent bodies in other countries have not adopted it in toto, it has been a major influence.