In 1938, the United States Congress appropriated funds for the acquisition of land for the construction of a new naval medical center, and President Franklin D. Roosevelt selected the present site in Bethesda, Maryland, and exterior design for it, on July 5, 1938.

Ground was broken by John McShain Builders for the Naval Medical Center on June 29, 1939, by Rear Admiral Perceval S. Rossiter, and President Roosevelt laid the cornerstone of the Tower on Armistice Day, November 11, 1940.

In 1945, at the end of World War II, temporary buildings were added to accommodate up to 2,464 wounded American sailors and Marines.

Since Roosevelt, most presidents have used a military hospital close to Washington, D.C., either Bethesda or Walter Reed AMC, as the primary facility for their medical care and that of their immediate family.

[17] Thus, when Johnson went under anesthesia for his procedures in 1965 and 1966, presidential authority was temporarily relegated to Vice President Hubert Humphrey according to their own agreement.

[13][15] On December 18, 1968, Johnson was hospitalized with "an upper respiratory infection with a slight bronchial irritation" during the so-called Hong Kong flu pandemic.

[20] On July 13, 1985, President Ronald Reagan underwent surgery to remove a cancerous polyp from his colon at the medical center.

[24] On October 17, 1987, First Lady Nancy Reagan underwent a mastectomy to treat breast cancer at the medical center.

[25] On May 14, 2018, First Lady Melania Trump underwent an embolization, a minimally invasive procedure that deliberately blocks a blood vessel in order to treat a benign kidney condition.

[30] In August 1960, a $5.6 million expansion project was initiated and consisted of two five-story wings attached to the main building's east side.

The original Naval Medical Center tower was since listed on the National Register of Historic Places by the U.S. Department of the Interior.

That merged facility was to be staffed by Army, Navy, and Air Force medical personnel and become the core of an integrated military medicine system in the National Capital Region (NCR).

The original 2005 estimate of the cost of shutting down WRAMC, and shifting it across town to Bethesda, and other locations, was "just under $900 million", according to Brian Lepore of the Government Accountability Office.

WRNMMC serves as the location of the headquarters for the National Capital Region Medical Directorate, a tri-service task force providing command and control for most medical treatment facilities in the District of Columbia and Northern Virginia, Maryland, Pennsylvania, West Virginia, and New Jersey.