Whiteman AFB began as Sedalia US Army Air Corps Glider Base, a training field for cargo and troop gliders and paratroopers. The location was rapidly constructed in the first summer of the US's involvement in World War Two, construction beginning in May and substantially ending in August 1942, and went to work training glider pilots for the Waco troop or cargo glider, capable of carrying thirteen to fifteen men ( a squad) and packs or a quarter-ton of cargo, including a jeep or a 75mm howitzer. These gliders were tugged by a modified C-46 or C-47 cargo plane, which could also be used for paratroop drops. The demand for air-dropped troops and equipment grew rapidly, and Sedalia expanded to Sedalia Army Air Field, under I Troop Carrier Command, in November. Air-dropped troops and troop carrier glider pilots trained at Sedalia AAF were deployed in the Normandy Invasion, the Battle of the Bulge, the air assault across the Rhine, the North Africa campaign, the invasion of Sicily, Operation Market Garden, the massive late war airdrop Operation Varsity. In 1945 the war ended and Sedalia AAF was closed and the buildings abandoned.

The field remained inactive until 1951, when the Air Force Strategic Air Command selected Sedalia as the first all jet strategic bomber base. A general update of the base was in order, and the runways were repaired, new military family housing was built, ground facilities improved, and a pool and gymnasium constructed. The 340th Bombardment Wing was transferred to Sedalia in 1954, soon flying B-47 Stratojets and KC-97 Stratotankers.

In 1955 Sedalia AFB was renamed Whiteman Air Force Base to honor local hero 2d Lt. George Allison Whiteman, one of the first US aviation fatalities in World War Two, at Pearl Harbor, shot down while taking off in response against the Japanese attack.

In the 1960s Whiteman AFB was substantially modified to become a major missile base, housing Minuteman missile silos, adding even more housing, mainly dormitories, a missile command center, and additional security police facilities. The Minuteman missiles at Whiteman upgraded repeatedly as the Minuteman series advance to the mark II and then to the mark III.

In the early 1990s Whiteman AFB was selected as the first deployment site for the new B-2 Spirit stealth bomber. From then until now Whiteman has been the home for the Spirit bombers, under the wings of the 503rd Bomb Wing, the first and eldest nuclear trained unit in the world - the 509th being the unit that performed both atomic bomb drops in World War Two. The B-2 Spirit Bomber is a lifting body aircraft, able to stealthily deliver a variety of munitions against any target, worldwide, from base. The first B-2 arrived at Whiteman in 1993, and soon sortied in support of US-NATO operations to protect civilians in Yugoslavia.

In 1994 Whiteman also gained the 442d Fighter Wing, which flies the legendary A-10 Thunderbolt II "Warthog." The 442d is descended from troop carrier units, originally activated at Sedalia in World War Two. In 1995 the last Minuteman III missiles were deactivate at Whiteman, finishing the conversion of the base from missile base to flying base.

In the 21st Century Whiteman AFB continues to look forward as a cutting edge of Air Force operation, with the assignment in 2010 of the 20th Reconnaissance Squadron, flying unmanned observation drones and transfer of the base to the Global Strike Command.