What is today the Walter Reed National Military Medical Center began as military hospitals for Army and Navy, mainly Walter Reed Medical Center (which had several names prior to the current one) and the National Naval Medical Center or Bethesda Hospital. Walter Reed himself was an Army doctor in the late 19th Century, responsible for tracking down the cause of yellow fever, a dangerous disease spread by mosquitos, and researched the causes of typhoid fever, spread partially through bodily fluid contact. Major Reed's work led to improved sanitary methods and insect control, saving a huge number of lives. He also created clinics for Army men suffering various illnesses.

In the 1920s, the Army began to invest more seriously in a dedicated medical branch. Before the order by General John Pershing establishing the Army Medical Center, the military generally had doctors and surgeons attached to units. Long term issues were either dealt with by private physicians, or just tolerated. By the time World War II broke out, the Army had a developed system for treating the wounded, and a central hospital for treating disease, long term wounds, and medical issues other than combat wounds.

The Navy side of this history is shorter; like the Army, prior to the 1930s most Navy medicine was conducted by ship's doctors or at shore facilities. President Franklin D. Roosevelt had been Secretary of the Navy at one point in his career and saw a need for a central hospital for Navy personnel. The National Naval Medical Center was begun in 1938 and was up and running by the time the US entered World War II.

Both sides of the Center were dedicated to military personnel, but each has been pleased to be the treatment site for many US Presidents for major and minor issues.

The two centers were merged in 2008 and expanded to include Air Force medical professionals, as a result of BRAC efforts to control military administration costs.