Dr. Orton was born in Columbus, Ohio, and received his B.A. from Ohio State University (1901), his M.D. from the University of Pennsylvania (1905), and his M.A. from Harvard (1906). He served as a pathologist at St. Ann’s Hospital in Anacanda, Montana (1908–10) and later joined the staff of Worcester (MA) State Hospital as a pathologist, serving as Clinical Director until 1914. During 1913, he was an instructor in neuropathology at Harvard. After 1914, he spent three years as the Pennsylvania Hospital's Psychiatric Director.
In 1919, Dr. Orton was appointed Professor of Psychiatry and Director of the State Psychopathic Hospital in Iowa City, Iowa, where he remained until 1927, when he went to New York to serve as a neuropathologist at the New York Neurological Institute and as Professor of Neurology and Neuropathology at the College of Physicians and Surgeons. In 1939, he resigned because of ill health. In 1932, Dr. Orton was President of the Association of Research in Nervous and Mental Diseases and received an honorary degree of D.Sc. from the University of Pennsylvania in 1945.
Dr. Orton served as President of the American Psychiatric Association (1928–29).