Sheppard Matthew Walker was born in Perkinston, Mississippi to Columbus and Drucilla Cooper Walker. He obtained his Bachelor of Science degree from Western Kentucky University in 1932. He graduated with a PhD from Louisiana State University in 1941, and he was assistant professor of physiology at Washington University School of Medicine, St. Louis, MO before coming to UofL in 1949. At UofL he was Chair of the Department of Physiology and Biophysics in the School of Medicine. He married Emma Christine Jenkins. He was 50-year member of the American Physiological Society, and winner of The Commonwealth Fellowship in 1962.