The F-35B‘s pilot ejected the jet and survived the crash, which is the first in the history of the hugely expensive weapons programme.
“It‘s a total loss,” a US Marine Corps official said.
Images posted on social media showed a plume of black smoke rising above the crash site in Beaufort.
The Marine Corps later confirmed the incident in a statement, saying the “pilot safely ejected from the single-seat aircraft and is currently being evaluated by medical personnel”.
Image: The F-35B is used for short take-offs and vertical landings
Officials added that there were no civilian injuries.
Launched in the early 1990s, the F-35 is the largest and most expensive military programme of its type across the globe.
Unit costs vary, but F-35s cost around $100m (£76.6m) each.
Britain currently has 15 F-35Bs, but has in total from American aviation giant Lockheed Martin.
Image: Donald Trump has praised the highly expensive F-35 programme
Earlier this week, two F-35Bs for the first time.
The family of single-seat, single-engined, all-weather multirole fighters are designed to perform ground-attack and air-superiority missions.
It has three main models, and the F-35B variant is for short take-offs and vertical landings.
The crash comes a day after the US carried out its first operation using the F-35B against Taliban targets in Afghanistan.
The Israeli military announced it had used the F-35A to carry out two separate strikes in May.
US President Donald Trump has praised the F-35‘s “super stealth” technology.
He said in July: “This is an incredible plane. It‘s stealth - you can‘t see it.
“So when I talk to even people from the other side, they‘re trying to order our plane. They like the fact that you can‘t see it. I said, ‘How would it do in battle with your plane?‘”