Governor AG Brown made the first public proposition to establish a hospital for the insane in 1846. In 1848, the Mississippi Legislature appropriated funds for the original facility, which opened in 1855 at the present site of the University of Mississippi Medical Center in Jackson. In 1900, the name of the hospital was changed from "Mississippi State Lunatic Asylum" to "Mississippi State Insane Hospital." In 1935, the psychiatric hospital was moved to the community of Howell which was then the site of the state penal colony. Located near the current towns of Brandon, the area was renamed "Whitfield" in honor of Gov. Henry L Whitfield.
When it opened on March 4, 1935, the main hospital and buildings covered the 350 acres it presently occupies. The remainder of the 3,333-acre tract was devoted to general farming, dairying, pastures, orchards and truck farms [i.e., vegetable fields] during the early and mid-1900s. Seventy of the more than 100 buildings on campus were constructed between 1926 and 1935. They were built along a cottage type plan in a colonial design with red brick and white columns and trim. Some were built with a cupola on top. The last original cupola still sits atop the administration building and has become the logo for the hospital.