Joint Base San Antonio was created out of an Army fort and several Air Force installations. The oldest of these was Army fort Sam Houston, originally established in Alamo City as a Quartermaster Depot in 1845. The post later relocated to a parcel of land donated by the citizens of San Antonio in 1876, and became a permanent military installation fourteen years later.

The Apache war chief Geronimo was imprisoned at the Sam Houston Quadrangle, on what is now JBSA grounds, for about six weeks in 1886, before being transferred to various Army posts around the West.

From 1910 until World War II, Sam Houston was the largest Army post in the United States, and was the training grounds to many outstanding American soldiers, including Dwight D. Eisenhower, who was stationed here at the start of World War II.

At the end of World War II, the decision was finalized to make this post the main Army medical training facility. In the years following, the Brooke General Hospital was built, and the Institute of Surgical Research, the Burn Center, the Medical Field Service School, and Health Services Command were established.

One of the facilities of JBSA, Randolph Field is one of the oldest fields in the US military, and one of the earliest and most carefully planned of all air bases from before the Cold War. In 1926, with the conversion of the US Army Air Service to the US Army Air Corps; the Air Corps Act provided for the expansion of the Air Corps, with purchase of new aircraft, ground facilities, and an increase of personnel.

In assessing the needs of the Air Corps, General Frank P. Lahm, "the nation's first military aviator," in charge of flying training for the Air Corps, recognized the Air Corps required a new training center. The general appointed a committee of five officers to plan a new airfield; this committee was presented with unsolicited initial plans by 1st Lt. Harold Clark, a motor pool officer with pre-military career training as an architect, for a radical and futuristic airfield using concentric circular design with quadrant sections, between two runways aligned with prevailing winds. Gen. Lahm was impressed and reassigned Lt. Clark to finalize his design. This was done in 1927, and a site was scouted and selected. The new field was named for Captain William Millican Randolph, who had been on the name selection committee when killed in a crash in 1928. Construction began in November 1927, and continued through 1931, with dedication in 1930. 1931 saw the relocation of the Air Corps Training Center, School of Aviation Medicine, and various other flying schools to Randolph, and the Primary Flying School opened at Randolph in November 1931. Randolph Field had become the "West Point of the Air."

Randolph Field trained thousands of pilots through basic and primary flight training in the 1930s, with increasing numbers as the global political situation of the decade became more tense. At that time law required that 90% of the commissioned officers of the Air Corps be rated pilots, and so nearly all officers of the time went through Randolph for training. The training demands of the later 1930s were so great the Air Corps contracted primary training to civilian instructors, leaving basic flight to the Randolph school.

In 1935 Randolph Field was the setting and shooting location for the Hollywood film West Point of the Air, starring Wallace Beery, with Robert Young, Lewis Stone, Maureen O'Sullivan, Rosalind Russell, and Robert Taylor, all stars of their era.

In June 1941 the Army Air Corps became the Army Air Force, and in December the USA was plunged into World War Two. Randolph Field trained pilots as fast as practical, with specialized pilot training conducted at many other fields and bases around the country. In 1943 Randolph instituted the Central Instructor's School, and trained over 15,000 instructors before the end of the war.

The post-War and Cold War saw a series of training transfers through Randolph, including combat crew training, helicopter training, and instrument training. Recently, Randolph AFB has been the central aviation training center for instructor training and refreshing/recurrency, navigator and combat systems officer training (CSO training since transferred out), and has supported Marine and Navy aerial navigation training. Electronic Warfare Officer training was added to Randolph's portfolio in the post BRAC Air Force.

Lackland began in 1941 as a field for Kelly Field, then one of the Army Air Corps main training centers. In later 1942 Lackland was separated from Kelly, named San Antonio Aviation Cadet Center, and assigned the mission of training Air Force cadets, instructing pre-flight trainees. This mission continued through the war. In 1947 San Antonio was renamed after Brigade General Frank Lackland, and became the only basic military training facility for the newly minted US Air Force.

In 1951, Lackland became one of the original sites for Air Defense Command's radar station network, a function now transferred to the Federal Aviation Administration.

Over the next twenty years Lackland's training facilities and mission expanded and contracted, and training periods varied, eventually settling on 6 weeks and 16 training squadrons. Language courses and other non-technical training have come and gone, but the basic training mission has only varied once, in 1966, due to a medical crisis.

JB San Antonio was formed in 2010 when US Army Fort Sam Houston, Randolph Air Force Base and Lackland Air Force Base were merged together as part of the 2005 BRAC.