Construction at Fort Sam Houston began in the mid-1870s under the supervision of the military commander of the Department of Texas, Major General Edward Ord, a West Point-trained army engineer.

The significant contributions of Fort Sam Houston to the United States were recognized in 1975 when the post was designated as a National Historic Landmark.

The Sundry Civil Service Bill of 3 March 1873 included a $100,000 allotment for a new army post in San Antonio, on 93 acres of land deeded by the city on Government Hill.

[4]: 15  Included on the Quadrangle was a combination 87 feet (27 m) tall watchtower and 6,400 US gal (24,000 L) water tank designed by General Montgomery C. Meigs, based on one he had seen in Europe, and which he called "his work of art".

[4]: 17, 18 In 1880, fifteen officers' quarters were designed by architect Alfred Giles, west of the Quadrangle, and bordering a parade ground.

[6] The Quadrangle is now an office complex housing the commanding general and staff of U.S. Army North as well as the Fort Sam Houston Museum.

The base has maintained the historical integrity of the post's different sections, which represent different eras of construction, and reflect various Army concepts in planning and design.

At the end of World War II, the Army decided to make Fort Sam Houston its principal medical training facility.

As a result of the Base Realignment and Closure Commission (BRAC) 2005 recommendations, all military medical training has been consolidated at Fort Sam Houston.

The Navy moved its medical training from San Diego, California; Great Lakes, Illinois; and Portsmouth, Virginia.

Fort Sam Houston has also initiated public–private partnerships to renovate and adaptively reuse significant historic buildings.

In June 2006, the San Antonio Express-News reported that Fort Sam Houston received utility disconnection notices due to budget constraints.

The United States Postal Service operates the Fort Sam Houston Post Office at 1804 Stanley Road.

[15] Several notable figures have served at the fort, including Arthur MacArthur Jr., Leonard Wood, Benjamin Foulois, Frederick Funston, and John J.