Seale Harris Sr. studied medicine at the University of Georgia from 1891-1892 and at the University of Virginia from 1892 to 1894, receiving his M.D. from the latter. Harris operated a private practice in Alabama until his appointment to the Chair of Medicine at the Medical College of Alabama in Mobile in 1907.

In 1917, Harris was commissioned a Major and assigned to the staff of General William Crawford Gorgas in the Surgeon General's Office. He served during World War I in Europe from May 1918 to March 1919, investigating food conditions and nutritional diseases. He was later appointed to Lt. Colonel as a member of the Research Committee of the American Expeditionary Forces in France. Upon leaving the service in 1919, Harris was promoted to the tank of Colonel in the Medical Reserve Corps.

Dr. Harris sold the Southern Medical Journal to the Southern Medical Association and used the profits to build a hospital, named the Gorgas Hotel Hospital, in Atlanta in 1924. The same year, he presented a paper on 'The Food Factor in Pellagra' to the International Conference on Health Problems in Tropical America. He was named Medical Man of the Year in 1949 and awarded the Distinguished Service Medal of the American Medical Association for his discovery of hyperinsulinism.