It was formed in 1900 in Dallas, Texas as University of Dallas Medical Department. It allied with Baylor University in Waco, Texas in 1903 and moved to the Texas Medical Center in Houston, Texas in 1943.

In 1969, Baylor College of Medicine separated from Baylor University under the direction of Dr. Michael E. DeBakey.

Currently, 168 medical students join the medical school each year, 75% of which are from Texas.