UNT Health Science Center was initially founded in 1970 as the Texas College of Osteopathic Medicine (TCOM).

In 1971, TCOM students secured ownership of Taverner Bowling Alley,[5] located next door to the osteopathic hospital, renaming the structure the "Basic Science Building."

[8] In 1990, TCOM opened the DNA Identity Laboratory, with the responsibility of assisting the state of Texas in evaluating paternity cases.

[9] In 2009, the UNTHSC opened a Doctor of Physical Therapy (DPT) and PhD in Public Health Studies degree program's.

[11][12] In 2013, UNTHSC began developing an inter-professional education (IPE) program, in participation with Texas Christian University (TCU).

In 2013, HSC launched Fort Worth's first Mobile Pediatric Clinic to deliver health care to children living in underserved parts of the city.

The first year consists of introductory basic science (e.g. anatomy, biochemistry, genetics, and immunology) integrated with physiologic processes structured by body system (cardiovascular, pulmonary, hematologic, musculoskeletal, renal, neurologic, and endocrine).

During this time, students also learn physical examination, doctor-patient interactions, and the principles of osteopathic, palpatory diagnosis and manipulative therapy.

After learning the physiologic foundations during the first year, the second-year curriculum shifts focus to disease processes and pathology, which are also organized by body system.

[26] TCOM's systems-based, two-pass preclinical curriculum, piloted by Bruce Dubin, DO, Associate Dean of Academic Affairs, has remained the same since conception in 2010 and is now widely replicated at sister osteopathic medical schools (e.g. RVUCOM, KCUMB-COM, etc.).

[28] Annual tuition fees since 2020 have covered a 6-month subscription to USMLE World ("UWorld") and TrueLearn ("COMBANK") test bank questions.

In an annual report by George W. Bush Institute (2020), TCOM was ranked #1 amongst U.S. medical schools for innovation impact productivity, a measure of how well an institution converts research inputs (e.g. research spending) into patents, licenses, startups, widely cited papers, and graduates.

In 2022, HSC received $4.8 million in funding from Tarrant County and City of Fort Worth to start a physical therapy-focused accelerator program with Techstars, a global investment business firm.

Equity investments into the startup companies will be made by HSC and Goff Capital to total nearly $10 million for the project over three years.

[40] Ten early startup companies focused on driving innovation in human movement are participating in the Accelerator's 3-month program.

The companies are matched with mentors and undergo a rigorous program that prepare them for Demo Day, where startups present their newly curated pitches to venture capitalists, angel investors, foundations and family offices.

Clinicians range from a variety of medical and surgical specialties and subspecialties, including audiology, allergy/immunology, family practice, cardiology, dermatology, gastroenterology, neurology, obstetrics & gynecology, optometry, osteopathic manipulative treatment, pediatrics, physiatry, psychiatry, speech language pathology, and sports medicine.

[42] Through TCMHCC, HSC child psychiatrists provide assessment and behavioral telehealth visits to at-risk children and adolescents and telehealth-based consultation and training to pediatricians and primary care providers requiring clinical assistance to identify and treat mental health issues in their patients.

Supported by state funds and private donations, the institution purchased land east of the osteopathic hospital along Camp Bowie Boulevard to form a permanent campus in 1972.

[44] The 2018 Campus Master Plan, the most recent institutional roadmap, shows potential at full build-out for over 2.3 million gross square feet of space.

[46] In June 2022, HSC unveils its Immersive Regional Simulation Center, which will be located on the first floor of the Gibson D. Lewis Library.

As a collaborative training hub for residency program trainees, clinical staff, emergency medical service providers, nursing home staffers, and HSC students, the $6.75 million facility will enable clinical programs within the region to incorporate virtual reality into their health care curriculum.

[47] The HSC Regional Simulation Center will house 14 clinic exam rooms; a large, changeable procedural skills suite; an “activities of daily living” suite resembling the inside of a home; several multipurpose “teams” rooms; and several learning lounges, where students can study.

Many of the rooms will be capable of being resized, remodeled, and adapted based on the needs of students and veteran health care workers.

Before 2022, TCOM was the only Texas public medical school to grant admission to undocumented persons (Non-Resident Aliens), including Deferred Action for Childhood Arrivals ("DACA") recipients.

[49] During 2021–22, UNTHSC has 157 registered student organizations (RSOs), the largest of which are Pediatrics Club, Emergency Medicine Interest Group, and American College of Osteopathic Family Physicians.

[51] The institute also received a $50 million award in 2020 from NIH to lead the coordinating center for the Artificial Intelligence/Machine Learning Consortium to Advance Health Equity and Researcher Diversity (AIM-AHEAD) program.