Starting in 1945 as 100-bed emergency hospital for civilian casualties under the Philippine Civilian Affairs Unit or PCAU-5, JRRMMC gradually transformed into a 450-bed teaching, training medical center.

On August 1, 1945, it was renamed North General Hospital (NGH) and placed under the control and supervision of the Bureau of Health.  In 1947, it became a training hospital under the Department of Health.

By virtue of R.A. 4264 passed on June 1965, NGH was renamed Dr. Jose R. Reyes Memorial Hospital in honor of Dr. Jose R. Reyes, its Chief of Hospital from March 16, 1948 to January 24, 1964.  On December 3, 1982, Executive Order No. 851, renamed it JOSE R. REYES MEMORIAL MEDICAL CENTER.

On January 31, 1987, E.O. 119 which provided the reorganization of the Department of Health, included the integration of the National cancer Control Center (as Department of Radiotherapy) and Dermatology Research Center. Again, on May 24, 1999, by virtue of E.O. 102, two services from DOH, Medical Infirmary (MEDI) and Dental Health Services were integrated with JRRMMC.