Fairchild AFB began in 1942 as Spokane Army Air Depot, a facility for repairing serviceable aircraft returned from the Pacific Theater in World War Two. This depot was selected for its accessibility to the Pacific and shielding by the Cascade Mountains, and the donation of land from the citizens of Spokane. The close of World War Two did not see the depot inactivated; the development of nuclear bombs created a need for long range strategic bomber facilities in the northern United States, and Spokane Army Air Depot was upgraded to base the most advanced fighter of the day, the B-29 Superfortress. 1948 brought a new name, Spokane Air Force Base, and soon additional bomber units were transferred to the new base. In 1950 Spokane Air Force Base was renamed to honor recently deceased General Muir Stephen Fairchild, World War One Air Corps pilot and later Vice Chief of Staff for the Air Force.

Fairchild AFB served as home base for the 92nd and 98th Bomber Groups, which were soon deployed to service in the Korean War. By the end of the 1950s the base was upgraded to house Atlas missile sites and air defense Nike-Hercules surface-to-air missiles. In the early Cold War Fairchild AFB had roughly half the nuclear weapons in the US arsenal. As the Cold War developed, in-flight refueling became increasingly important for flight operations, and Fairchild's strategic position made it an excellent in-flight refuelling base, and facilities at the base were expanded, although the ICBM mission wound down. Fairchild was the home base for units supporting Operations Young Tiger and Arclight, many bombing missions in Vietnam, and later many refuelling missions in support of Operations Desert Shield and Desert Storm.

Beginning in 1966 and continuing to the present Fairchild began housing the Air Force survival school for isolated crew in any environment, currently under the 336th Training Group. This school operates in close coordination with the 36th Rescue Flight, a search-and-rescue unit, which often sharpens skills through aid to civilians in need of rescue service and transport.

The winding down of military forces after the end of the Cold War reduced many units, but Fairchild's location made it an ideal tanker hub, and its critical support role in maintaining the global military air bridge. Fairchild units have supported countless missions since the Cold War, particularly in support of Operations Iraqi Freedom and Enduring Freedom.