The National Association for the Study of Epilepsy and the Care and Treatment of Epileptics was organized in New York in 1898 under the guidance of William Pryor Letchworth, L.L.D. and Frederick Peterson, M.D. Membership was for "any person interested in the scientific study of epilepsy, or in the study of ways and means to improve the condition of epileptics, or in sociological subjects generally." The first meeting was held May 14–15, 1901, in Washington, DC. 

The National Association became the American affiliate of the International League Against Epilepsy (ILAE) when the ILAE was established in August of 1909 in Budapest, Hungary. The National Association ceased to exist as an autonomous society in 1925. All members were also members of the American Psychiatric Association (APA), and in 1927 at the Minneapolis APA meeting, the National Association became the first organized APA section — the Section on Convulsive Disorders.

The American Branch of the ILAE was re-organized on May 12, 1936, at the time of the American Medical Association meeting in Kansas City, MO. The members of the American Branch were those principally concerned "with research and with treatment of extramural patients" in contrast to the Section on Convulsive Disorders whose members were concerned with institutional care of patients. In May of 1936, the American Branch held a joint scientific session with the Section on Convulsive Disorders.

Following World War II, a joint meeting was held December 13, 1946 in New York City of the American Branch ILAE, the ILAE and the Association for Research in Nervous and Mental Diseases (ARNMD). This meeting was a significant event for all the societies and has been used as the founding date of the AES.

Over the years, the AES has taken steps to implement our purposes by developing educational courses and symposia. In 1984, a special task force was appointed to see how the Society could attract basic neuroscientists. In addition, Investigators' Workshops were organized to integrate basic neurosciences into the life of our Society. In 1988, a concerted effort began to address issues on Childhood Onset Epilepsy and to shape our Society into an active, rather than a reactive mode, by identifying educational and investigative priorities.