The US Federal Aviation Administration issued a flight ban to Syria and Syrian airspace on Monday.
The FAA cited threats from armed extremist groups with anti-aircraft weapons, as well as a lack of demand to fly into the region.
"Armed extremist groups in Syria are known to be equipped with a variety of anti-aircraft weapons which have the capability to threaten civilian aircraft," the FAA said in a statement issued to pilots. "Opposition groups have successfully shot down Syrian military aircraft using these anti-aircraft weapon systems during the course of the conflict."
The ban overrides a previous FAA notice strongly suggesting against flying into Syria.
Now, any flight wishing to enter Syrian air space will need to contact the FAA and receive approval.
The FAA's statement comes as the Islamic State continued its encroachment into Syria. It does not appear to be related to Syria's civil war, in which 170,000 people have been killed over the past three years.
Currently, American flights flights to Iraq or above Iraqi airspace are also restricted amid fighting in the country with the Islamic State.
On July 22, a flight ban to Israel was issued during Operation Protective Edge after a Gazan rocket hit a city close to Ben-Guion Airport.