Laughlin AFB started, like many Air Force facilities, as a training base in World War Two. The base was named for a local pilot, Jack T. Laughlin, killed in action in a B-17 over the Makassar Strait in what is today Indonesia. Laughlin mainly trained pilots and crews for the B-26 Marauder, a difficult to fly, fast, well armed, medium range medium weight bomber with a bad handling reputation. Despite its reputation, only two Marauders, of roughly five thousand, were lost in combat in US service. In the remaining two years of the war Laughlin was regraded from Air Base to Field, and again to Auxiliary Field, and closed at the end of the war.

The base reopened in 1952, in a period of increasing international tensions, to train pilots with the new F-80 Shooting Star and F-84 Thunderjet, mainly in the T-33 training jet. Five years later, Laughlin was transferred to Strategic Air Command, and gained the 4080 Strategic Reconnaissance Wing, which provided high-altitude reconnaissance using the RB-57D Canberra and the more famous U-2. The U-2 that provided photographs of Soviet missiles in Cuba was headquartered at Laughlin, as was later U-2 pilot Major Rudolf Anderson, the first recipient of the Air Force Cross (posthumous).

Much of the later history of Laughlin is not publicly available, but from the early 1970s to the present Laughlin returned to and increased its training mission, starting with the reactivation and assignment of the 47th Flying Training Wing to the base. The base today conducts undergraduate pilot training for the USAF, Air Reserve, and allied and friendly air forces, graduating 20 to 30 pilots per year.