Archibald Byron Macallum was born in Belmont, Ontario, Canada. His academic training was obtained at the University of Toronto, where he received his B.A. in 1880, and Johns Hopkins University, where he received his Ph.D. in 1888. For several years he was a lecturer on physiology at the University of Toronto, and then he became professor of physiology in the Faculty of Medicine in 1891. While at Toronto, Macallum founded and chaired the Department of Biochemistry, the first biochemistry department in Canada and one of the first in the world. Macallum is also credited with the organization and extension of the medical school at Toronto in the early 1900s, and he was a strong advocate for the construction of the original medical building. As part of the war effort, he left the University of Toronto in 1916 to head the Advisory Committee for Scientific and Industrial Research, which became the National Research Council of Canada, and served as its first president. In 1920, Macallum went to McGill University to become the first chairman of the Department of Biochemistry. He retired in 1928 after a distinguished scientific career.
Macallum's research was influential in its time. His early research on the microchemical distribution of inorganic ions within cells contributed to the knowledge of the localization of calcium, potassium, and iron in plant and animal tissues. Later, as an active member of the Biological Board of Canada, he carried out fieldwork at its marine stations and compared the absolute and relative concentrations of the inorganic elements in seawater and in the body fluids of many animals. From this work he developed his theory that the body fluids of animals represent living "fossil" evidence of the ancient ocean environments in which they had evolved.
In recognition of his contributions to science, Macallum received the unusual honor, for a Canadian, of election to fellowship in the Royal Society of London in 1906 and was president of the Royal Society of Canada from 1916 to 1917.He was part of the small group who organized the American Society of Biological Chemists and served as the Society's president for two terms, in 1912 and 1913.