Founded during World War II, the medical school was initially housed in a handful of abandoned barracks.

The present campus site on Harry Hines Boulevard was occupied in 1955 upon the completion of the Edward H. Cary Building.

In November 1972 the name and scope of the medical school were changed with its reorganization into The University of Texas Health Science Center at Dallas.

In 1987 the John D. and Catherine T. MacArthur Foundation gave the university 30 acres (120,000 m2) near the South Campus for future expansion.

A 20-year master plan for the site, designed by Edward Larrabee Barnes and John MY Lee and Partners,[11] called North Campus, called for six research towers, a support-services building, an energy plant, and underground parking, in addition to the Mary Nell and Ralph B. Rogers Magnetic Resonance Center and the Moncrief Radiation Oncology Center.

In 1999 the university purchased an additional 50 acres from the MacArthur Foundation, and a portion was used to create an on-campus student-housing complex of 156 apartments.

[12] Also in 2008, UT Southwestern acquired the Exchange Park site and renamed it the Paul M. Bass Administrative and Clinical Center on the North Campus.

The center was named in honor of Mr. Bass, chairman emeritus of the Southwestern Medical Foundation, who served in that role until 2008.

With this property, the campus grew to 9 million square feet of laboratory, clinical, educational, and administrative space, covering 387 acres.

The building is the largest LEED (Leadership in Energy and Environmental Design) silver-certified laboratory space in Texas.

[14] In March 2022, a $100 million gift, made by the O’Donnell Foundation, endowed a new school of public health.

The Doris and Harry W. Bass Jr. Clinical Center for Heart, Lung, and Vascular Disease is a collaborative effort between UT Southwestern faculty and community physicians.

In 2022 alone, UTSW faculty is training about 3,800 medical, graduate, and health professions students, residents, and postdoctoral fellows.

The Medical School features six Academic Colleges that function as small learning communities, each headed by a faculty mentor.

The combined degrees include: With an enrollment of more than 1,000 students (549 predoctoral and 484 postdoctoral), the Graduate School educates biomedical scientists, engineers, clinical researchers, and counselors.

[10] The clinical training curriculum includes coursework in the disciplines necessary to understand human disease at the level of cellular physiology and biochemistry.

[23] UT Southwestern Medical Center is one of seven health systems in the United States being recognized for its leadership development initiatives to internal employees.

[43] The Health Sciences Digital Library and Learning Center supports the information needs of UT Southwestern's research, educational, and clinical activities.

The Library and Learning Center maintains a large collection of electronic information resources, print archives, rare books, and materials concerning the history of medicine.

[44] UT Southwestern scientists and physician researchers conduct investigations into cancer, stem cells, neuroscience, heart disease and stroke, arthritis, diabetes, and many other fields.

Also at the Institute are voice specialists, rehabilitation experts, and neuroimmunologists, plus basic and translational scientists in cellular and molecular neuroscience, neurobiology, regenerative medicine, neuro-engineering, imaging, and genetics.

[47] Located on the UTSW campus, CRI is home to an interdisciplinary group of scientists and physicians pursuing research in regenerative medicine, cancer biology and metabolism.