The selection of the site for the Barracks was a matter of personal interest to President Thomas Jefferson, who rode through Washington with Lt. Col. William Ward Burrows, the second commandant of the Marine Corps, in search of a suitable location. The site now occupied was approved due to its proximity to the Washington Navy Yard and because it was within easy marching distance of the Capitol.

The early 19th-century Barracks was arranged in a quadrangle as it is today, and the use of the building was similar. The areas on the south and east side of the quadrangle were used for offices, maintenance facilities and living spaces for troops, and a building on the west was the location of the officers' quarters. The Home of the Commandants at the north end of the Barracks was completed in 1806 and is the only original building still standing. It is the oldest public building in continuous use in the Nation's Capitol. The rest of the Barracks was rebuilt between 1900 and 1907.

The training of new officers and recruits started at the barracks soon after it was established and continued throughout the 19th century. Until 1901, it was also the location of Marine Corps Headquarters. Marines from the Barracks participated in the defense of Washington in the War of 1812, and served in the Indian Wars of 1826-37, the war with Mexico, the Civil War and the Spanish American War. Most recently, Marines from the Barracks deployed to Southwest Asia and participated in Operations Desert Shield and Desert Storm.

The Barracks has also been home to the United States Marine Band since 1801. Shortly after its formation, the band was requested to play for President John Adams at the Executive Mansion. This White House engagement began a tradition which became so established that today the names "Marine Band" and "President's Own" are synonymous. It was at the Barracks that John Philip Sousa, during the time he was the director of the Marine Band, wrote many of his immortal marches.