Huxley (no relation to T. H. Huxley or any of his descendants) was born at Birkenhead near Liverpool. He studied physics at Cambridge University where he obtained his PhD in 1952 after wartime research on the development of radar. Like many other physicists after the war Huxley was interested in applying physics to biological problems. After two years in America at the Massachusetts Institute of Technology and the period 1956–61 at the biophysics unit of the University of London, he returned to Cambridge to join the staff of the Medical Research Council's molecular biology laboratory, where he remained until 1987. In 1988 he became director and professor of biology at Brandeis University, Boston. He also served from 1988 to 1994 as director of the Rosenstiel Basic Medical Sciences Research Centre.

In 1953, in collaboration with Jean Hanson, Huxley proposed the sliding-filament theory of muscle contraction. This was based on his earlier study of myofibrils, the contractile apparatus of muscle, with the electron microscope. He found that myofibrils are made of two kinds of filament, one type about twice the width of the other. Each filament is aligned with other filaments of the same kind to form a band across the myofibril, and the bands of thick and thin filaments overlap for part of their length. The bands are also linked by an elaborate system of crossbridges. When the muscle changes length the two sets of filaments slide past each other. Further, the two sorts of filaments can be identified with the two chief proteins of muscle, myosin in the thick filament and actin in the thin. This made possible an elegant solution to how muscles contract at the molecular level.

In the areas where both kinds of protein are in contact, Huxley suggested that one, most probably myosin, serves as an enzyme, splitting a phosphate from ATP and so releasing the energy required for contraction. He concluded that the evidence of the combination of actin and myosin is seen in the bridges between the two kinds of filaments.

The theory has since been much enlarged and taken to deeper levels of molecular understanding. Despite this, the basic insight of Huxley and Hanson has remained intact.