It was built as Naval Air Station Sanford, a Master Jet Base for carrier-based attack and reconnaissance aircraft, and was used by the U.S. Navy until 1969.

[3] Since 2008, however, a majority of its passenger traffic has been domestic; this is attributable to the entrance of Las Vegas–based Allegiant Air, for which Sanford is a focus city.

[4] Sanford was also a small focus city for the travel marketer Direct Air until the company's demise in 2012.

For the next twenty-five years, the airport was a general aviation facility and periodically hosted civilian/military air shows and static displays.

OLF Osceola was transferred to the control of Seminole County, Florida, but was never officially recommissioned as an active airfield.

Following a major drug interdiction by local and federal law enforcement agencies, Seminole County placed large speed bumps at various intervals across the runways to deter future illegal use.

Charter airlines catering to the heavy British tourist demographic that had previously been using Orlando International Airport were offered greatly reduced landing fees at Sanford, and therefore many carriers relocated their operations.

In 2010, Allegiant Air announced it was moving many flights to the larger and more centrally located Orlando International Airport in order to compete with AirTran Airways.

[6] In October 2017, Monarch Airlines ceased operations, after entering administration, therefore resulting in the termination of their flights to Sanford.

In 2024, the airport secured a $13 million loan to improve on key infrastructure projects to enhance operations.

The Seminole County Sheriff's Office has a hangar and support facility for aviation elements of the agency's Special Operations Division.