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

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

Since its 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 its 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.