Hamilton was educated at the universities of Cambridge and London. He served as a lecturer in genetics at Imperial College, London, from 1964 until 1977 when he moved to America to take up an appointment as professor of evolutionary biology at the University of Michigan. He returned to England in 1984 to serve as a Royal Society Research Professor at Oxford.

In the Origin of Species (1859) Darwin raised a “special difficulty,” which he at first considered unsurmountable. How could natural selection ever lead to the evolution of neuter or sterile insects? Darwin's answer was that selection may be applied to the family, as well as the individual. In a series of papers, beginning in 1964 with The Genetical Theory of Social Behaviour, Hamilton has pursued these implications and opened the way for the emergence of sociobiology. The key concept deployed by Hamilton is that of inclusive fitness, which covers not only an individual's fitness to survive but also the effects of his behavior on the fitness of his kin.