Moody Army Air Base was activated June 1941, and named for Major George Putnam Moody, an Air Force pioneer, who had been killed only a month earlier while test flying a Beechcraft AT-10 Wichita two-engine trainer aircraft. Moody AAB was immediately put into service, with a mission of training flight cadets in two-engine flying, a challenge in a day when most aircraft in service were single-engine, and most aviators in the Army Air Force were freshly minted, including many of the instructors. The instructors had to be thoroughly checked on twin-engine craft before being allowed to train, delaying the training process. Many of the training aircraft at Moody AAB were in fact the AT-10, the same plane Major Moody had been test flying. Moody AAB also trained Bombardier and Navigators, and as the war continued became a POW camp, housing 490 German servicemen, relocated from Camp Blanding, Florida. By the end of the war Moody was mainly training light bomber pilots and crew. The end of the War in August 1945 led to the inactivation of Moody AAB in August of 1946.

Inactivation does not mean closure, and while on standby status Moody was redesignated Moody Air Force Base in early 1948, reassigned to Continental Air Command in late 1948, then reactivated in late 1949, and put through a construction and modernization program, adding permanent housing and offices, and extending and strengthening runways to handle the new jet planes and heavier bomber aircraft of the Cold War era. The main mission of the rebuilt Moody AFB was pilot instrument training, at first in support of US needs in the Korean War. Moody also gained a mission training jet interceptor pilots, flying some of the fastest tactical jets available at the time, the F-89 Scorpion and F-94 Starfire. Interceptor pilots training included mock runs on US bombers and transport aircraft going about their normal operations or training flights; on the receiving end, the target aircraft gained experience as targeted craft.

Interceptor training transferred away from Moody in 1960, and the base trained allied foreign pilots, particularly South Vietnamese pilots, from the early 1960s to the early 1970s. In 1975 Moody AFB transferred from Air Training Command to Tactical Air Command, the first time the base had not had a training mission; the squadrons now assigned to Moody were mainly air-to-ground attack squadrons. This mission continued to the end of the Cold War.

In 1992, Moody AFB was reorganized and reassigned to Air Combat Command, and several units from Homestead AFB were transferred to Moody following the destruction of Homestead by Hurricane Andrew. Force realignment in the 1990s continued, and Moody became the home of an airlift squadron and several fighter squadrons, and later new rescue squadrons. Continued reorganization had returned a training mission to Moody AFB, which was later inactivated; Moody is also home to a rescue group, security forces group, and air-ground operations group.