Purdue University Airport was the very first university-owned airport in the United States. In 1930, inventor-industrialist David E. Ross (one of two people for whom Purdue's Ross–Ade Stadium is named) donated a tract of land to be used as an aeronautical education and research facility at Purdue University.

The U.S. government designated Purdue University Airport as an emergency landing strip on November 1, 1930.

Runway 5/23 was paved later in the 1930s.

Amelia Earhart prepared her airplane for her around-the-world flight attempt in Hangar 1 at the airport. Earhart was an adjunct faculty member at the time, and the Lockheed Model 10 Electra she flew was purchased for her by the Purdue Research Foundation.

Hundreds of members of the U.S. Army, Navy, and War Training Service were trained at Purdue Airport during World War II, as were several commercial pilots from Latin America. In 1955, the airport became the home of the first Reserve Officers' Training Corps flight training program.

The original hangar, now known as the Niswonger Hall of Aviation Technology, still stands and is used by Purdue University's Department of Aviation Technology as offices, classrooms, and laboratories. The bay that held Earhart's plane still contains aircraft that are used by the Aeronautical Engineering Technology program for maintenance and inspection training. A large addition to the building was completed in the summer of 2009. A plaque on the building near the side entrance commemorates the airport's history.

In the early 60s, runway 10/28 and a larger hangar were built to support the Midwest Program on Airborne Television Instruction with two DC-6 aircraft.

From 1942 through 1971 Purdue University also had its own airline based at the airport, first known as Purdue Aeronautics Corporation and later Purdue Airlines. Originally operating Douglas DC-3 aircraft and then Douglas DC-6s, it finally operated three McDonnell Douglas DC-9-30 jet aircraft. The airline also operated a further DC-9 on behalf of Playboy founder Hugh Hefner as his private jet, "The Big Bunny", also based at the airport.

Evergreen International Airlines maintained a short-lived cargo operation at the Airport in the late 1970s using Lockheed L-188 Electra turboprop aircraft.

President Ronald Reagan and Air Force One (then a military version of a Boeing 707) visited Purdue University Airport on April 9, 1987. He later wrote a letter concerning a list of questions to the editor of the Purdue Exponent concerning his optimism about the future of relations between the United States and the Soviet Union and his favorable impression of what he saw at Purdue.

Following the loss of regularly scheduled airline service in 2004, airport administration shifted focus to the needs of the university's aviation technology programs. Airline service at the airport resumed in May 2024.