In 1993, the airport, which, at the time, would be the largest airport in Mindanao, was built mainly on a fund granted by the United States Government amounting to US$47.6 million through its United States Agency for International Development (USAID). The Philippine Government, through the Department of Transportation and Communication (DOTC), has co-shared 25% of the total project cost of the airport. It is strategically situated on a 5,994,577-square-meter (599.4577 hectares) plot of high-altitude, government-owned and formerly leased pasture land in Barangay Fatima approximately 14 kilometers (8.7 mi) away from the central business district of General Santos. It was rumored that the construction of the airport was part of a forward strategy of the US Military forces in the Philippine Islands in an, accordingly, apparent attempt to reestablish their presence in Southeast Asia. This allegation came out a few years later after the Americans' eviction from their installations at Subic Naval Base, Olongapo, and Clark Air Base, Pampanga in 1992. Both the U.S. and the Philippine governments denied the allegation.

Upon the opening of the new airport in 1996, it has since gotten hold of the record as the biggest airport facility in the island of Mindanao, which has then become a very promising addition to the potential of the city in its bid to become a "Boom Town"—which means rapidly developing urban center—as it was indeed dubbed as is during the time. All flights, in small aircraft, to and from Iloilo and Cebu cities by the national flag carrier Philippine Airlines (PAL) that were previously operating in the old and smaller Buayan Airport has since then landed and departed in this new and far better airport facility. On the first few weeks of operation of the new airport, PAL has initially deployed its Boeing 737-300 aircraft to serve its special direct flights to and from the capital to serve the travel needs for the ongoing Palarong Pambansa sports event being held during the time. As before there were no direct flights going to and from the capital of Manila to General Santos as PAL could not utilize its wider body and long range aircraft to safely land and take off in the city's old and smaller Buayan Airport. At that time there were only two options for air travelers to get to Manila from General Santos and vice versa. One was to fly to Mactan–Cebu International Airport and wait for a connecting flight to Manila upon arrival in Cebu, or secondly, make a tiresome and lengthy 4-hour overland journey to Francisco Bangoy International Airport in Davao City to catch a direct flight to Manila and vice versa.

Philippine Airlines commenced regular thrice weekly direct flights to and from Manila using a bigger and wider Airbus A300B4 aircraft. Later, this became five times weekly in November 1996. And four months after its launch, a daily service was in effect in December 1997 while maintaining its existing regular frequencies to and from Iloilo and Cebu cities using smaller Fokker 50 aircraft. The airline's initiative to commence a direct flight to and from the capital has helped pave the way to continually increase not only the air passenger traffic coming in and out of city's own airport, but also air cargo traffic, which is indicative of the city's vibrant tuna export industry and fast growing economy in general. However, PAL's financial difficulties in the late 90s forced the halting of its Iloilo and Cebu routes out of General Santos International Airport in 1998, leaving PAL with only its single daily frequency to and from Manila to operate in the airport. In 1997, Air Philippines (now PAL Express) commenced its daily Manila–General Santos–Manila flight using Boeing 737-200 and McDonnell Douglas MD-88 aircraft.

The first international chartered flight to land in General Santos International Airport was of former President Fidel V. Ramos' homecoming from one of his state visits abroad in the mid-1990s. Aboard PAL's Airbus A340 aircraft, the president and his party landed in General Santos International Airport directly from Bangkok, Thailand. In November 2003, international flights to and from Manado, Indonesia were also briefly operational on a regular weekly frequency to this city by an Indonesian carrier Merpati Nusantara Airlines using Fokker 70 aircraft. PAL has also disclosed plans of commencing international flights to and from General Santos in the late 1990s.

Cebu Pacific, the Philippines' largest low-cost carrier, commenced daily flights to and from Manila on October 2, 2006. Initially served by Airbus A319 aircraft, it has since been upgraded to the A320, A321, and A330 aircraft.

With the 48-hour shutdown of Francisco Bangoy International Airport in Davao City on June 2–3, 2013 due to an accident involving a Cebu Pacific aircraft from Manila, General Santos International Airport handled most of the diverted flights from Davao for the stranded passengers going to and coming from Manila, Cebu, Zamboanga and Kalibo cities.

Bigger aircraft such as the Boeing 777 come to the airport due to tuna cargo and increase of passengers.

Plans to rehabilitate and expand the airport were laid in 2015.