Before construction of the Greenville–Spartanburg International Airport (GSP), each city had its own airport and competed for airline service. In the mid-1950s Roger Milliken, a textile heir, industrialist, and businessman (CEO of Milliken & Company), worked with other upstate business leaders to get a shared airport for the two cities. In 1958, a proposal for an airport between the two cities was presented to the legislative delegation for the two counties, which approved the construction and the creation of an airport commission, headed by Milliken.

GSP opened on October 15, 1962, replacing Greenville Downtown Airport as the primary airline destination in the region. Delta Air Lines, Eastern Air Lines, and Southern Airways had all been serving both Greenville and Spartanburg separately; however only Eastern and Southern moved to the new GSP airport, while Delta discontinued their service.

In the 1980s, GSP expanded its terminal and cargo facilities, and the runway was lengthened twice in the 1990s. In 2004, the airfield was named for Milliken.

Having been served by legacy carriers, with large hubs in nearby Atlanta and Charlotte, GSP had long been plagued with high fares. The arrival of low-cost carriers reduced fares and increased passenger figures. Allegiant Air began flights to Florida in 2006, and in 2011 Southwest Airlines began service to five cities.

Local officials attribute Southwest's presence to an unprecedented 38% growth in passenger figures between 2010 and 2011. In 2011, GSP received an ANNIE Award from Airline and Airport News & Analysis for being the fastest-growing small airport in the United States. In 2012 the U.S. Department of Transportation's Bureau of Travel Statistics reported that average fares from GSP decreased by 14%; the largest decrease in the country.