Dr. MacDonald was born in Niles, Ohio and educated at Iron City College (1865-66), in Pittsburgh, Pa. He received his M.D. degree from Bethune Hospital Medical College in New York (1869). He was awarded an honorary L.L.D. in 1917 and received an honorary A.M. from Union College in 1894. He served in the sixth cavalry during the Civil War.
Dr. MacDonald served as Assistant Physician and later Visiting Physician to the Kings County Hospital and Almshouse (1869–83), was Medical Superintendent of the Kings County Lunatic Asylum (1873–75), and was manager of the New York State Lunatic Asylum in 1879. He was Superintendent of the State Asylum for Insane Criminals in 1881 and later affiliated with Dr. MacDonald’s Sanitarium for Mental Nervous Diseases in Central Valley, New York.
He was President of the New York State Commission on Lunacy (1889–96), Professor of Mental Diseases at Bellevue Hospital Medical College (1888–87), Lecturer at Albany (NY) Medical College (1892–94), and consultant to the Manhattan State Hospital. He served as an examiner of the mental condition of the assassin of President McKinley in Buffalo, NY, and also in the trial of Henry David Thoreau in 1907. Dr. MacDonald was President of the American Medico-Psychological Association (1913–14).