Service by Southwest to Orlando International ends Aug. 11 and one of two daily flights to Baltimore Washington International ends Sept. 28.
Allegiant Air offers several direct service flights from GSP into Orlando-Sanford.
Southwest will maintain daily nonstop flights to and from GSP at Chicago Midway, Houston and Nashville.
GSP is undergoing a $120 million terminal improvement that is projected to increase passenger traffic to two million by the year 2030.