Tyndall AFB began as Tyndall Field, in January 1941, named for a Florida native, World War One US military pilot, 1st Lt. Frank Benjamin Tyndall, Silver Star recipient, who shot down four German enemy fighters over France; Lt. Tyndall was killed in service in 1930. Tyndall Field opened as a flexible gunnery school, training bomber gunners.

Tyndall gained its first troops on December 7, 1941, the same day as the attack on Pearl Harbor that drew the US into war. In the next four years Tyndall trained thousands of gunners, including many Allied troops; notably Free French and Chinese nationals. The most famous trainee though Tyndall was Hollywood film star, Oscar-winning Best Actor, Clark Gable, enlisted 1943, and a five mission combat gunner/observer.

The end of the war brought demobilization, after a brief transfer to Tactical Air Command, the renamed Tyndall Air Force Base was transferred to Air University and became a school for pilot instructors, ground control intercept operators, and interceptor pilots and aircrew. Naturally, this period also saw an upgrading of base housing, runways, and ground facilities.

The Cold War kept Tyndall busy. In 1956 Tyndall installed new radar systems to support both strategic and tactical interception missions. In 1962 Tyndall became a stepping stone base for aircraft streaming to the Cuban Missile Crisis, and maintained an interception position for the Caribbean thereafter. In 1979 Tyndall AFB was transferred to Tactical Air Command again, providing training support and, in 1981, hosting the 325th Fighter Wing.

After the Cold War, Tyndall was shifted from command to command for a short period, under the base and force adjustments of that period, finally stabilizing under Air Education and Training Command. The 325th Fighter Wing became the base host unit, and it continues to be host. In 2003, the 325th Fighter Wing became the first unit assigned the F-22 Raptor, the most highly advanced fighter plane in the world.