In Columbus he quickly specialized in treating mental disorders and management of people suffering from insanity. He was once stated that if he could fix his eyes on those of even the most violent lunatic he could control him without difficulty, an accomplishment which he succeeded in doing several times. He was a common witness in court to cases of doubtful insanity. Both he and Marmaduke B. Wright were members of the Ohio General Assembly. Together they promoted a bill which later became law in 1835 in which Ohio insanity cases would come under the care of the state.
William Maclay Awl then was acting superintendent of the "State Hospital", which opened in 1838. Also in 1838 he was president of the Association of Superintendents of Asylums for the Insane of the United States and Canada. He held this position until 1851. He headed a bill which founded schools for the education of the blind and feeble-minded in Ohio. In addition, in 1846, he, Daniel Drake, and other leading members of his field to establish the Ohio State Medical Society.