The military reservation was established in 1791 on about 28 acres (110,000 m2) at the tip of Greenleaf Point. Major Pierre (Peter) Charles L'Enfant included it in his plans for Washington, the Federal City, as a major site for the defense of the capital.
An arsenal first occupied the site and defenses were built in 1794. However, the fortifications did not halt the invasion of British forces in 1814, who burned down many public government buildings in Washington, D.C. during the War of 1812. Soldiers at the arsenal evacuated north with as much gunpowder as they could carry, hiding the rest in a well as the British soldiers came up the Potomac River after burning the Capitol. About 47 British soldiers found the powder magazines they'd come to destroy empty. Someone threw a match into the well and "a tremendous explosion ensued," a doctor at the scene reported, "whereby the officers and about 30 of the men were killed and the rest most shockingly mangled." The remaining soldiers destroyed the arsenal buildings, but the facilities were rebuilt after the war. Land was purchased north of the arsenal in 1826 for the first federal penitentiary. The conspirators accused of assassinating president Abraham Lincoln were imprisoned there, tried by military commission and, after being found guilty, four were hanged and the rest received prison sentences. Among those hanged was Mary Surratt, the first woman ever executed under federal orders.
One of the buildings on the complex, Ulysses S. Grant Hall, is the location of the 1865 military tribunal of the conspirators of the assassination of Abraham Lincoln. The Hall periodically holds public open houses, where each quarter of the Hall is open to the public and people can visit the courtroom and learn more about the trials. A hospital was built next to the penitentiary in 1857, and wounded Civil War soldiers were treated at what then was called the Washington Arsenal. The arsenal was closed in 1881, and the post was transferred to the Quartermaster Corps.
A general hospital, the predecessor to the Walter Reed Army Medical Center, was located at the post from 1898 until 1909. Major Walter Reed found the area's marshlands an excellent site for his research on malaria. Reed's work contributed to the discovery of the cause of yellow fever. Reed died of peritonitis after an appendectomy at the post in 1902. The post dispensary and the visiting officers' quarters now occupy the buildings where Reed worked and died.
About 90 percent of the present buildings on the post's 100 acres (0.40 km2) were built, reconstructed or remodeled by 1908. In 1901, with the birth of the Army War College, the post, now called Washington Barracks, became the army's center for the education and training of senior officers to lead and direct large numbers of troops. Its first classes were conducted in 1904 in Roosevelt Hall, the iconic building designed by the architectural firm of McKim, Mead and White. The Army Industrial College was founded at McNair in 1924 to prepare officers for high level posts in Army supply organizations, and to study industrial mobilization. It evolved into the Industrial College of the Armed Forces. The post was renamed as Fort Humphreys in 1935 (a name previously assigned to today's Fort Belvoir, VA). The Army War College was reorganized as the Army-Navy Staff College in 1943, and became the National War College in 1946. The two colleges became the National Defense University in 1976.