The construction of military s after the Pearl Harbor Attack that caused the entry of the United States into World War II resulted in the construction of the Smoky Hill Army Air Field (AAF) on 2,600 acres (1,052 ha), southwest of Salina, Kansas. The first unit associated with the airfield was the 376th Base Headquarters and Air Base Squadron, whose engineers first laid out the base in April 1942. Construction began in May 1942 with the aid of nearly 7,000 workers. The airfield was activated on September 1, 1942, and was assigned to the II Bomber Command, Second Air Force.

Enough construction was completed that the 376th moved into facilities on September 10. The first aircraft to arrive, Boeing B-17 Flying Fortresses, arrived later that month and were assigned to the 346th Bombardment Group. The mission of Smoky Hill AAF was that of a Second Phase Heavy Bomber Operational Training Unit (OTU). In the second phase of training, combat groups formed in the first phase focused on the teamwork of the full combat crew, such as bombing, gunnery, and instrument flight missions. Upon completion, the groups moved on to the third phase, the final level of training before overseas deployment to the combat theaters.

In April 1943, the 49th Aviation Squadron arrived at Smoky Hill; the all-African American unit included mechanics, electricians, and aircraft handlers but no pilots. The 366th was joined by the 400th Bombardment Group in the training mission at Smoky Hill AAF on July 31, 1943. The 366th concentrated on B-17 Flying Fortress training; the 400th on B-24 Liberator training.

On March 21, 1946, as the Army Air Forces underwent significant restructuring, the airfield was transferred to the Fifteenth Air Force, then part of the Strategic Air Command. Then in January 1948, following the formation of the United States Air Force, the airfield was renamed Smoky Hill Air Force Base.

As postwar budgets declined, the base was eventually closed and turned over to the Air Materiel Command late in 1949.

As the Air Force's needs grew during the Korean War, the base was reactivated on August 1, 1951. The base hosted the 310th and 40th Bombardment Wings.

On March 16, 1957, the base was renamed Schilling Air Force Base, in honor of Colonel David C. Schilling.

Throughout 1964, rumors circulated that the base was being considered for a shutdown. In November, Defense Secretary Robert McNamara announced that Schilling AFB, along with 94 other military installations, would be closing. The shutdown began in 1965 and was completed in 1967.

The airport was the takeoff and landing point for the Virgin Atlantic GlobalFlyer, flown by Steve Fossett in the first nonstop, non-refueled solo circumnavigation of the earth from February 28 to March 3, 2005. In 2006, Fossett embarked on another such flight in the GlobalFlyer, again departing and arriving Salina, from March 14 to 17, 2006. This time he broke the world record for distance over a closed circuit without landing, which he had set a month prior.

Salina Regional Airport has memorialized the records set by Steve Fossett with Fossett Plaza. The plaza has a memorial, seating area, plaques with the story of the Global Flyer and Steve Fossett, and a viewing area to observe operations.

Historical airline service

Salina received its first scheduled airline service in the early 1930s by United States Airways, which flew a Metal Aircraft Flamingo on an airmail route between Denver and Kansas City, stopping at Goodland, Salina, and Topeka, Kansas. This route was discontinued about 1933 and airline service did not return to Salina until 1949.

Continental Airlines then began stopping at Salina with Douglas DC-3s in 1949, also on a route between Denver and Kansas City, making as many as ten stops at smaller cities throughout Colorado and Kansas. Continental's service continued until 1961.

Central Airlines replaced Continental in 1961, also using DC-3s, but later upgrading with Convair 240 and Convair 600 aircraft. In 1967 Central merged into Frontier Airlines which used Convair 580s, and in early 1978 introduced Boeing 737 jets to Salina on flights to Denver and Chicago, the latter making three stops en route. The Chicago flights were later replaced with service to Kansas City, and Frontier was soon flying all 737 jets through Salina up to four times per day. All Frontier service ended on January 6, 1983.

Air Midwest first began service to Salina as an air taxi in the late 1960s, with flights to Wichita using Cessna 402s. The carrier suspended service for a few years, then returned from 1972 through 1976 with flights to both Kansas City and Wichita using Beechcraft 99s. Air Midwest returned again in 1983 to replace Frontier's service with flights to Denver, Kansas City, and Wichita, using Fairchild Swearingen Metroliners; however, the Denver flights were soon discontinued.