The Brown-Séquard Society began in 1931 as a group to "encourage scholastic attainment and to strive for the general advancement of medicine by honoring students of exceptional ability and leadership." The society is named for 19th-century physician, Dr. Charles-Édouard Brown-Séquard (1817-1894), a Mauritian physiologist and neurologist. Brown-Séquard was a member of the Medical College of Virginia (MCV) faculty from 1854-1855, serving as the Professor of Institutes of Medicine and Medical Jurisprudence. It was during this time that he wrote the paper "Experimental and Clinical Researches on the Physiology and Pathology of the Spinal Cord and Some Other Parts of the Nervous System." It is in this paper that Brown-Séquard Syndrome, a neurological condition that can occur due to an incomplete spinal cord injury, was first described in medical literature. Ultimately, Brown-Séquard left MCV due in part to his abolitionist stance regarding enslavement.

The society selected members from the School of Medicine junior and senior classes who maintained a B average or above. Election to the society required a unanimous vote by the current members. As part of their activities, the society began the annual Brown-Séquard Lecture in 1936. In 1940, the society petitioned to form a chapter of Alpha Omega Alpha (AOA) Medical Honor Society at MCV, with the Brown-Séquard Society becoming the Beta Virginia chapter of the honor society. The AOA remains active at the VCU School of Medicine.