Born at Kempten in Germany, Mayr was educated at the universities of Griefswald and Berlin, where he obtained his PhD in 1926. He then served as assistant curator of the museum there before moving to America in 1932. After spending many years at the Museum of Natural History, New York, he moved to Harvard in 1953 to serve as Agassiz Professor of Zoology, in which post he remained until his retirement in 1975.

As a field zoologist Mayr has worked extensively on the birds of the Pacific. Beginning with his New Guinea Birds (1941), he published a number of surveys and monographs on the ornithology of the area.

He is, however, better known for such works as Systematics and the Origin of Species (1942) and Animal Species and Evolution (1963) in which, at the same time as such other scholars as George Simpson and Theodosius Dobzhansky in America and Julian Huxley in Britain, he attempted to establish a neo-Darwinian synthesis. The enterprise has continued to hold together fairly well against the onslaughts of such critics as Motoo Kimura and has so far absorbed, without major upset, the massive inflow of data from the new discipline of molecular biology.