Luke AFB is named for the number two US ace to fly in World War One, 2nd Lt. Frank Luke, Jr., the first aviator Medal of Honor recipient, with 18 aerial victories, KIA after a three victory run on German observation balloons, having been shot down behind enemy lines and wounded; approached by German soldiers, Lt. Luke drew a pistol and defended his position to the death.

The first Luke air field was in Hawaii, and was renamed Naval Air Station Ford Island after the US Army Air Corps request to name the new Arizona air base after Lt. Luke. The Arizona site was selected in 1940 after an offer from the city of Phoenix for a long term lease for the land for $1 per year. The original lease hold was for 1,440 acres; the current base covers roughly 1.9 million acres, roughly half the area of the state of Connecticut, and greater in area than the states of Delaware or Rhode Island.

The creation of Luke Field was part of the greater military buildup before World War Two; Luke was assigned to fighter pilot training, and was already training before completion in July of 1941. The first class graduated in August of 1941, the first 45 of over 12,000 to graduate from Luke in the next four years.

With the close of the war Luke Field was inactivated, and remained inactive until 1951, when the Korean War created a demand for pilots. Luke was activated under Air Training Command to train fighter escorts for bombers. From this point on, Luke grew. In 1953, Luke was the activation site for the 3600th Air Demonstration Team, generally known as the Air Force Thunderbirds.

In the later 1950s Luke AFB was transferred to Tactical Air Command, and the 4510th Combat Crew Training Wing squadrons were upgraded to the F-100 Super Sabre. Most of the pilots graduated from this period, from the early 1960s to the early 1970s, went on to flying combat missions over Vietnam.

The constantly updating nature of fighter technology led to a great many fighter model changes over the years, but Luke has remained a leading fighter aircraft training center. From the 1960s through the 1980s Luke AFB trained pilots from allied and friendly nations, particularly from the Republic of China (Taiwan) and the Federal Republic of Germany (West Germany). In 1993 another notable achievement at Luke was the graduation of 1st Lt. Jeannie M. Flynn and her qualification for the F-15 Eagle, the first female combat fighter pilot in US Air Force service.

The end of the Cold War brought a great deal of force realignment and to the Air Force and Luke AFB, but the need for fighter training continues to this day. Since the early 1980s Luke has been a training center for the F-16 Fighting Falcon, having trained the first two F-16 squadrons, an association strengthened by base realignment; Luke is now the exclusive F-16 training base. Pilots from Luke have flown sorties for Operations Desert Shield and Desert Storm, and in support of the Global War on Terrorism, particularly Operation Enduring Freedom, and in support of Operation Iraqi Freedom.