Ellsworth AFB began as Rapid City Army Air Base, established in January 1942 as a training location for B-17 Flying Fortress units. The base was rapidly constructed and training began by the end of summer. Thousands of pilots, gunners, radio operators, and navigators were trained at Rapid City AAB, until the end of World War Two. Rapid City was then used as a training center for weather reconnaissance and combat squadrons. The base was closed in the post-war lull, for six months, until the rising tension of the Cold War prompted increased readiness, and the base was reopened. Rapid City Air Force base was briefly renamed Weaver AFB in 1948, in honor of Brig. Gen. Walter Weaver, but this was reversed due to massive public request. The base was again renamed in 1953, in honor of Brig. Gen. Richard Ellsworth, and newly the renamed base was dedicated by President Eisenhower in a personal visit. Ellsworth AFB was now assigned front line, ready alert bombers, beginning with D-36 Peacemakers, continuing with B-52 Stratofortresses in 1955, making the base a keystone in US airspace defense.

Starting in 1960, Ellsworth became a base for newly fielded Titan I intercontinental ballistic missiles, which cycled through a short lifespan by 1963. Unlike many AFBs with Titans in the early 1960s, Ellsworth updated their ICBM facilities to Minuteman I missiles in the mid-1960s, and again to Minuteman II missiles in the early 1970s. Ellsworth's central role in first strike defense kept the base highly alert through the Cold War, with a major upgrade in facilities in the mid-1980s and the rotation of the B-52 out of service, replaced by B-1B Bones.

The end of the Cold War saw a rapid reduction in operation at Ellsworth, and in September 1991 the always ready units were ordered to stand down. Post-Cold War reorganization led to a new role for Ellsworth, and the base shifted from a strategic bombardment mission to a worldwide conventional munition delivery mission, with a new focus on tactical training. The missile silo system was also deactivated and the missiles removed. New national strategic requirements in the 2000s required additional mission realignment, but Ellsworth AFB remains active in US air defense.