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Originally formed as the 15th Medical Regiment on 18 October 1927. Reorganized as the 65th Medical Regiment in Fort Oglethorpe, Georgia and activated June 1, 1941.
On March 10, 1944, the Regiment was broken up and redesignated the 65th Medical Group, with its organic companies becoming separate numbered Medical Collecting and Medical Clearing Companies. The Group served in Normandy,
Northern France, Rhineland, Ardennes-Alsace, and Central Europe.
The Group was reactivated for service in Korea from 1958 to 1971.
On 15 October 2008, 18th Medical Command was redesignated as the 65th Medical Brigade. The headquarters was stationed at USAG Yongsan inside the Japanese Army Stockade until the end of 2017. It then moved to Camp Humphreys as part of the relocation of the Yongsan Garrison.