Franing Field, the site of the present Quad Cities International Airport, was picked as an ideal flying field, with 120 acres (49 ha) of level, grassy land free of obstacles. The airport made headlines right at the start, chosen as a control point for the first coast-to-coast flight in the fall of 1919. On August 18, 1927, an estimated 10,000 people came to welcome Charles Lindbergh in Moline and his famous plane, the Spirit of St. Louis, on the Gugenheim tour, a cross-country commercial aviation promotion tour. In 1929, Phoebe Omlie set an altitude record above the airport in a Velie Monocoupe, the only plane ever manufactured in Moline, which still hangs in the passenger terminal.

In 1947, the Metropolitan Airport Authority of Rock Island County was formed after seven townships voted to establish it.

In 1957, the first count of enplaning and deplaning passengers was made, with a total of 59,701 recorded.

The airport underwent major remodeling in 1961 and 1968, adding everything from baggage claim to a restaurant and boarding areas.

The present airport terminal was completed in 1985 after studies showed that an addition to the 1954 structure would be more costly than an entirely new terminal. The shift to the new $11 million terminal allowed expansion of airline facilities; between 1979 and 1986, the number of airlines increased from two to seven.

AccessAir, Air Midwest, AirTran Airways, America West Airlines, American Airlines, Allegiant Air, Chicago Air, Midway Connection, Northwest Airlines, Ozark Air Lines, Pan American World Airways, Skyway Airlines, Trans World Airlines, United Airlines, SkyWest Airlines, and Sun Country Airlines have flown to Quad Cities. At one time Mississippi Valley Airlines had its headquarters at the airport. In the early and mid-1990s turboprop equipment was common; Northwest Airlink and other airlines had Saab 340Bs. Carriers have replaced their turboprops with newer regional jets. Allegiant Air Airbus A319s and Airbus A320s fly to Orlando, Las Vegas, Clearwater, and Phoenix/Mesa.

None of the current legacy carriers fly mainline jets from Moline; the most recent mainline service was Delta Air Lines A319s and A320s to Atlanta in 2013. Until 2002–03, American Airlines MD-80s flew to Saint Louis after its acquisition of TWA in the early 2000s; TWA succeeded Ozark, which started flying to Moline in 1950. (Moline's first jets were Ozark DC-9s in 1966.)

United Boeing 727s and 737s flew non-stop to Denver until 1995; United flights to Moline began in the 1930s. Republic DC-9s flew to both Detroit and Minneapolis starting in 1986; successor Northwest pulled out in 1989. America West 737s flew to Phoenix in 1987–92, and Braniff served Moline from the 1940s until 1959.

In 2001, the terminal underwent a major renovation and expansion: two new concourses, a larger baggage claim area, new restaurants, and gift shops. The project doubled the size of the terminal. The Philadelphia architectural firm DPK&A designed the new concourses.

A larger U.S. Customs and Border Protection Facility was opened in 2014 in a former air cargo building. The facility processes international passengers arriving on general aviation flights. No airlines use this facility. It has a processing room, an interview room, space for agricultural inspections, office space, and holding cells for passengers who are prohibited from entering the U.S. or who are being detained and transported by law enforcement. Phase two of the project will renovate the remainder of the building to create an international terminal or Federal Inspection Service should the airport establish nonstop international charter flights. Gere-Dismer Architects of Rock Island designed the facility.

On March 30, 2021, the airport announced another major renovation at a cost of $20-$40 million. This renovation will update and expand the ticketing area, which was last updated in 1985. Other changes include a wider TSA screening area, an indoor/outdoor garden and observation deck with water feature, modern seating and power sources throughout the airport, and exterior solar panels above covered parking. The announcement coincided with a renaming of the airport from Quad City International Airport to Quad Cities International Airport along with a new logo. The architectural firm Alliiance, of Minneapolis, designed the renovations.

The airport received funding for this renovation in part from the 2021 Infrastructure Investment and Jobs Act. Upgrades are set to begin in 2023.

The airport set its passenger record in 2007 when 484,212 passengers boarded flights while 481,930 deplaned, for a total of 966,142. The total beat the record of 911,522 set the previous year. In 2008 passenger numbers declined: 957,087 passengers enplaned or deplaned. Passenger count dropped to 763,416 in 2013.