Mountain Home AFB, named for a local city in Idaho, opened as an Army Airfield in August of 1943 as a B-24 Liberator training center. It had been intended as a B-17 training center, but this mission was taken up by Moses Lake Army Airfield before Mountain Home activated. Liberator training kept Mountain Home busy, training the 470th Bombardment Group, the 490th Bombardment Group, and the 494th Bombardment Group, each in turn before deployment. Among these trainees was the future Senator from South Dakota, George McGovern, candidate for US President. Generally the Mountain Home training was the final training before deployment, and included mock combat exercises, with the Liberators targeted by American aircraft for additional realism, and to train US fighter pilots. Mountain Home converted to training the new powerful B-29 Superfortress, but the end of the war brought a fast decline in training, and Mountain Home Army Air Base inactivated in October of 1945.

Mountain Home was reopened as an Air Force base in 1948 as the home of the 5th Strategic Reconnaissance Group, which flew RB-29 Superfortresses, running long range, high altitude photographing and radiation detection missions into Soviet airspace. A plane from Mountain Home gained evidence of the first Soviet nuclear weapon tests in 1949, at the Semipalatinsk Test Site in what is today Kazakhstan.

Despite this, and other, achievements, the base was considered out of date for modern aircraft, and closed for reconstruction in 1950. After a year of reconstruction Mountain Home AFB was operational enough to reopen and was reassigned to the Air Resupply and Communication Service, which sounds like a fairly routine logistics group, but was in fact a highly classified psyops, guerilla warfare training, classified operation airdrop and air supply, and intelligence gathering unit, operating at that time in Korea. The 5th transferred to another base in 1953, and Mountain Home AFB was transferred to Strategic Air Command, as the base now had runways able to support long range very heavy planes. Soon Mountain Home was home for B-47 Stratojets and KC-97 Stratotankers. For a period from the late 1950s to the mid 1960s Mountain Home also housed Titan I intercontinental ballistic missiles, until these were phased out.

Mountain Home was reassigned from SAC to Tactical Air Command in the mid 1960s, a role it has kept since, although TAC was redesignated Air Combat Command in the early 1990s. Originally Mountain Home units were tactical reconnaissance, observing ground movements in Vietnam. In the early 1970s Mountain Home shifted to a tactical fighter wing base, now housing the 366th Fighter Wing, which has been the host unit, under various names, at Mountain Home for over 35 years. The 366th has relocated to various theaters over the decades, notably Iraq and Afghanistan, but always returns to its Mountain Home.