Raised in the rural community of Glenevis, Alberta, Vanderwolf went on to earn a BSc from the University of Alberta and completed graduate work with Donald Hebb at McGill University, completing his PhD in 1962.
Vanderwolf spent over 30 years at the University of Western Ontario in London, Ontario, during which time he published over 140 papers on the relation of hippocampal, neocortical, and pyriform cortical activity to behavior and the dependence of many of these brain-behavior relations on the activity of central neurons that release the transmitter substances acetylcholine and serotonin. His work also includes research on the brain mechanisms involved in olfaction. Vanderwolf's work is relevant to the problems of consciousness, memory, motor control and such human disorders as Alzheimer's disease and depression.
He has published two books, An Odyssey Through the Brain, Behavior and Mind and The Evolving Brain: The Mind and the Neural Control of Behavior that provide an overview of his academic career and research findings. In 2000, he was awarded an honorary degree from the University of Lethbridge.