In 1977, members of the College of Medicine's charter class of 32 students began their medical training in the basement of the Olin E. Teague Research Center on Texas A&M University's campus. The College was founded as part of Texas A&M University, with a basic science campus in College Station and a clinical campus in Temple.

In September 1997, the Texas A&M System Board of Regents approved organization of the health-related entities throughout the A&M System into one university –Texas A&M Health Science Center, which officially began operation on Sept. 1, 1999. Original academic units in the consolidation included College of Medicine, College of Dentistry, Institute of Biosciences and Technology, the then-proposed School of Public Health and School of Graduate Studies. Then, July 15, 2013, TAMHSC transitioned to become a unit of Texas A&M University.

Since the inaugural class of 1981, the College of Medicine has graduated more than 2,258 physicians. While the College has grown in size and scope, it remains true to the original mission of improving the health and well-being of the people of all communities through excellence in education, research and health care delivery. The College of Medicine now has campuses in five locations throughout the state of Texas.