The cutting-edge F-35B was completely destroyed in the crash, which is the first of its kind for the model.
Britain has ordered more than 100 of multi-million pound jets, which were described as “super stealth” by US President Donald Trump.
The pilot ejected and survived the crash, close the Marine Corps Air Station Beaufort, and is undergoing medical tests.
A US Marine Corps official said: “It’s a total loss.”
The Marine Corps said in a statement: ”The pilot safely ejected from the single-seat aircraft and is currently being evaluated by medical personnel.
«There were no civilian injuries. Marines from MCAS Beaufort are working with local authorities currently conducting standard mishap operations to secure the crash site and ensure the safety of all personnel in the surrounding area.»
The cause of the crash is under investigation.
Military officials said the jet was on a routine training exercise and was not trying to land at the time of the crash.
The UK has 15 F-35B jets, and has pledged to buy another 123 from the US.
The United States government has also announced plans to buy 2,600 of the jets.
They are the most expensive jets of their kind in the world.
Their exact costs are not known but F-35s cost £76.6m ($100m).
The F-35B is used for short take-offs and vertical landings.
A Marine F-35B carried out its first combat airstrike on Thursday. US airmen struck Afghanistan “in support of ground clearance operations”.