By 1785, the Dominican Friars put it on the priority list and despite the enthusiasm of Governor General Mariano Folgueras, the planned colleges failed to materialize until the late 19th century.

The faculty was founded in 1871 as the Facultad de Medicina y Farmacia by virtue of the modified Moret Decree of 1870 which supplants the Philippine educational reforms of 1865 by the Spanish Government.

[3] The haciendas of Colegio de San Jose were turned over to the University of Santo Tomas as ordered by Governor General Domingo Moriones y Muralla in 1879.

It was also associated with the San Juan de Dios Hospital which functioned as the faculty's clinical arm as decreed by King Alfonso of Spain on October 29, 1875.

[3] This setup continued until 1941 when the Japanese took over Quezon Institute and transferring all of its medical staff and patients to San Juan de Dios Hospital.

Clinical training during this time was in partnership with Saint Paul Hospital in Intramuros until the walled city's destruction during the Liberation of Manila.

The faculty offers the four-year Doctor of Medicine degree, a comprehensive professional academic program which combines lectures, case analyses, and practical simulation exercises.

Contrary to what was expected as a decline in the quality of the learning of students by some faculty members, the first and second batches of PBL-trained physicians garnered 92% & 96% passing percentages, respectively.

In the oral examinations, groups of three students each are questioned by panels composed of three professors on basic, clinical, and emergency medical sciences.

Medical school graduates qualify to take the licensure exams for physicians conducted by the Board of Medicine, and under the control and supervision of the Professional Regulation Commission of the Philippines.

Applicants must have graduated from Science, Technology, Engineering and Mathematics (STEM) or Health Allied academic strands in high school, or have completed an International Baccalaureate Degree program (IB) with Biology Higher Level Course with a predicted grade of 28 points.

The current Editor-in-Chief of the journal is Raymond L. Rosales, a neurologist from the faculty and a member of the External Scientific Advisory Board for the Collaborative Center for X-Linked Dystonia Parkinsonism (XDP) at Harvard Medical School.

Designed by Architects Manuel Francisco and Julio Victor Rocha, the building follows a Bauhaus style, and houses the largest auditorium in the University.

[17][18] In the same month, the groundbreaking rites for the construction of the Saints Cosmas and Damian Simulation and Research Center was also held in front of the Miguel de Benavides Library.

In February 2021, Manila city mayor Isko Moreno, approved the university's plan to hold face-to-face classes for the students of medicine and other health programs.