Born in Ottawa, Canada, Wilson was educated at the University of Toronto and at Princeton, where he obtained his PhD in 1936. After working for the Canadian Geological Survey (1936–39) and war service, he was appointed professor of geophysics at the University of Toronto (1946) where he remained until his retirement in 1974.

Wilson did much to establish the new discipline of plate tectonics during the early 1960s and was the first to use the term ‘plate’ to refer to the rigid portions (oceanic, continental, or a combination of both) into which the Earth's crust is divided. In 1963 he produced some of the earliest evidence in favor of the sea-floor spreading hypothesis of Harry H. Hess when he pointed out that the further away an island lay from the mid-ocean ridge the older it proved to be.

His most significant work, however, was contained in his important paper of 1965, A New Class of Faults and their Bearing on Continental Drift, in which he introduced the idea of a transform fault. Plate movement had been identified as divergent, where plates are being separated by the production of new oceanic crust from the mid-ocean ridges, and convergent, where plates move toward each other with one plate sliding under the other. Wilson realized a third kind of movement was needed to explain the distribution of seismic activity and the way in which the ocean ridges do not run in continuous lines but in a series of offsets joined by the transform faults. Here the plates slide past each other without any creation or destruction of material.

Wilson replied to critics of the plate tectonics theory, such as Vladimir Belousov, in his A Revolution in Earth Science (1967).