In 1941 the United States Army Air Corps built Napier Field, named in honor of Major Edward L. Napier of Union Springs, Alabama. One of the Army's first flight surgeons, he was killed in the crash of a Fokker D.VII, AS-5382, at McCook Field, Dayton, Ohio, on 15 September 1923. He had been a Medical Corps Officer in World War I and had transferred to the Army Air Corps. He was receiving training as a flight surgeon at the time of his death. The official report states that he was piloting the plane himself and there was a structural failure of a wing.

Napier Field was assigned to the Southeast Training Center of the Army Air Forces Training Command. It was commanded by the 73d Army Air Force Base Unit. In addition to the main facility, the following known sub-bases and auxiliaries were built to support the training operations:

Cairns Army Airfield 31°16′33″N 85°42′48″W

Wicksburg Auxiliary Field 31°19′10″N 85°40′25″W (now: Knox Army Heliport, Fort Rucker)

Dothan Auxiliary Field 31°14′28″N 85°26′36″W

Headland Auxiliary Field 31°21′51″N 86°18′56″W

Goldberg Auxiliary Field 31°24′50″N 85°27′36″W (now: Goldberg Stage Field, Fort Rucker)

Hyman Auxiliary Field 31°18′48″N 85°07′32″W

The 29th Flying Training Wing was activated at Napier on December 26, 1942. The 2116th (Pilot School, Advanced, Single-Engine) was main operational group at Napier Field. The group flew mostly AT-6 Texans as well as providing advanced & specialized training in single engine aircraft, including P-40 fighters. The first aircraft began operating on the field on October 1, 1941.

On December 20, 1941, the first group of British cadets arrived for training under the Arnold Scheme. The first American cadets graduated on July 3, 1942 (42-F). In late May 1945, officers from the Mexican Army began P-40 training at Napier Field.

The field was inactivated by the U.S. Army Air Forces on October 31, 1945, and the airfield and its improvements were made available to the City of Dothan and Houston County under an Agreement in 1946 which was jointly accepted. The airport lands lay dormant for about 20 years and Houston County later turned its share of Napier Field to the city.

In the early 1960s, a complete overhaul of the facility commenced with the old USAAF airfield layout being largely dug up and converted into reinforced hard surface for new jet runways, buildings and other facilities for a civil airport. Dothan Regional Airport opened to commercial activity on February 15, 1965.

In 2004 the Air Force returned to the airport in the form of a non-flying unit, the 280th Combat Communications Squadron (280 CCS), an Air Force Special Operations Command (AFSOC)-gained unit of the Alabama Air National Guard, which established Dothan Regional Airport Air National Guard Station on the airport.

Until 1965 the municipal airport was three miles west of town, where the Westgate Rec Center is now. It had three runways, all 4006 feet or less. Eastern Airlines stopped there from 1945 to 1964; Southern Airways arrived in 1956 and continued at the new airport.