The passengers are in the hospital in critical condition. The victims are yet to be named.
The Coroner's office said that officials are working on notifying next of kin. They say the pilots died from the blunt force of the crash.
One crew member 'died at the scene of the crash and the other at the hospital', according to Deputy Coroner Jeff Fowler said to WYFF-4.
Only three people were taken to Greenville Memorial Hospital following the crash as first responders worked on pulling the fourth from the wreckage.
At first one individual was reported to be seriously injured. Later Thursday afternoon a coroner confirmed two of the people on board had died.
"For some reason, we're not sure why, [the plane] was not able to stop, went off the end of the runway, and crossed to the grass on the runway, that's about another 200 feet, then down an embankment and finally came to rest at the airport road," police spokesman Donnie Porter announced after the crash.
"I believe that one of the pilots, not sure which, was either temporarily unconscious or what not but was leaning on the throttle," he added.
It's not clear where the plane was coming from, but it intentionally landed at the Greenville Airport, cops believe to pick up more passengers.
According to the Federal Aviation Administration's (FAA) website, the plane - a Dassault-Breguet Falcon 50 - is registered to Global Aircraft Acquisitions LLC of Lewes Delaware.
The plane fits between nine to 19 people.
Locals were warned to stay away from the airport as workers attended to the damaged plane that was leaking fuel as officials called it a Hazmat situation.
Officials also scrambled to turn off a still-running engine, that was successfully shut down by evening.
Greenville County Fire Department and EMS are on the scene, and officials are taking control the leaking fuel that could 'contaminate nearby streams'.
It's not clear how much fuel leaked from the craft.
Police spokesman Porter said that this was the biggest accident the airport has seen in a long time.
By Thursday evening the FAA was en route to take over the investigation.