MacPherson received his medical education from Methodist College and McGill University. MacPherson started the first St. John's Ambulance Brigade after working with the St. John's Ambulance Association.
MacPherson served as the principal medical officer for the first Newfoundland Regiment of the St. John's Ambulance Brigade during World War I. MacPherson began researching methods of protection against the poison gas and invented the MacPherson respirator (gas mask) in 1915, which was the first general issue gas countermeasure to be used by the British Army.
After suffering a war injury, MacPherson returned to Newfoundland to serve as the director of the military medical service and later served as the president of the St. John's Clinical Society and the Newfoundland Medical Association. MacPherson was awarded many honors for his contributions to medical science.