Beginnings

President Franklin D. Roosevelt's administration approved preliminary funds for site development of the Greater Cincinnati Airport on February 11, 1942. This was part of the United States Army Air Corps program to establish training facilities during World War II. At the time, air traffic in the area centered on Lunken Airport just southeast of central Cincinnati. Lunken opened in 1926 in the Ohio River Valley; it frequently experienced fog, and the 1937 flood submerged its runways and two-story terminal building. Federal officials wanted an airfield site that would not be prone to flooding, but Cincinnati officials hoped to build Lunken into the region's main airport.

Officials from Boone, Kenton, and Campbell counties in Kentucky took advantage of Cincinnati's short-sightedness and lobbied Congress to build an airfield there. Boone County officials offered a suitable site on the provision that Kenton County paid the acquisition cost. In October 1942, Congress provided $2 million to build four runways. Although the last of the land necessary to build the airport was not acquired until May 1943, site preparation had already begun. By mid March 1944, it had been named Greater Cincinnati Airport. The airport was to be "formally presented" to the City of Cincinnati in June.

The field opened August 12, 1944, with the first B-17 bombers beginning practice runs on August 15. As the tide of the war had already turned, the Air Corps only used the field until it was declared surplus in 1945. However, this was not before the first regularly scheduled air freight shipment in the United States arrived in mid-September, signalling the future importance of the airport.

On October 27, 1946, a small wooden terminal building opened and the airport prepared for commercial service. Boone County Airlines was the first airline to provide scheduled service from the airport and had its headquarters at the airport.

The first commercial flight, an American Airlines DC-3 from Cleveland, landed on January 10, 1947, at 9:53 am. A Delta Air Lines flight followed moments later. The April 1957 Official Airline Guide shows 97 weekday departures: 37 American, 26 Delta, 24 TWA, 8 Piedmont, and 2 Lake Central. As late as November 1959 the airport had four 5,500 ft (1,700 m) runways at 45-degree angles, the north–south runway eventually being extended into today's runway 18C/36C.

In the 1950s Cincinnati city leaders began pushing for expansion of a site in Blue Ash to both compete with the Greater Cincinnati Airport and replace Lunken as the city's primary airport. The city purchased Hugh Watson Field in 1955, turning it into Blue Ash Airport. The city's Blue Ash plans were hampered by community opposition, three failed Hamilton County bond measures, political infighting, and Cincinnati's decision not to participate in the federal airfield program.

Jet age

On December 16, 1960, the jet age arrived in Cincinnati when a Delta Air Lines Convair 880 from Miami completed the first scheduled jet flight. The airport needed to expand and build more modern terminals and other facilities; the original Terminal A was expanded and renovated. The north–south runway was extended from 3,100 to 8,600 ft (940 to 2,620 m). In 1964, the board approved a $12 million bond to expand the south concourse of Terminal A by 32,000 sq ft (3,000 m2) and provide nine gates for TWA, American, and Delta. A new east–west runway crossing the longer north–south runway was constructed in 1971 south of the older east–west runway. A fire on June 15, 1975, significantly damaged the old terminal building and killed two firemen.

In 1977, before the Airline Deregulation Act was passed, CVG, like many small airports, anticipated the loss of numerous flights; creating the opportunity for Patrick Sowers, Robert Tranter, and David and Raymound Mueller to establish Comair to fill the void. The airline began service to Akron/Canton, Cleveland, and Evansville. In 1981, Comair became a public company, added 30-seat turboprops to its fleet, and began to rapidly expand its destinations. In 1984, Comair became a Delta Connection carrier with Delta's establishment of a hub at CVG. That same year, Comair introduced its first international flights from Cincinnati to Toronto. In 1992, Comair moved into Concourse C, as Delta Air Lines gradually continued to acquire more of the airline's stock. In 1993, Comair was the launch customer for the Canadair Regional Jet, of which it would later operate the largest fleet in the world. By 1999, Comair was the largest regional airline in the country worth over $2 billion, transporting 6 million passengers yearly to 83 destinations on 101 aircraft. Later that year, Delta Air Lines acquired the remaining portion of Comair's stock, causing Comair to solely operate Delta Connection flights. In the meantime, the airport had been renamed Greater Cincinnati International Airport in November 1978.

In 1988, two founders of Comair, Patrick Sowers and Robert Tranter launched a new scheduled airline from CVG named Enterprise Airlines, which served 16 cities at its peak.