The attack on al-Tanf, where US troops are based, injures two allied Syrian opposition fighters, the coalition says.
A drone attack hit a US-led coalition base in southern Syria, the US military’s Central Command has said.
“Three one-way attack drones attacked the al-Tanf Garrison in Syria,” a CENTCOM statement said on Friday.
Two of the drones were shot down by the coalition, but the third hit the compound, wounding two allied Syrian opposition fighters who received treatment, the statement added.
“Attacks of this kind are unacceptable,” CENTCOM spokesperson Joe Buccino said, without specifying who carried it out.
“They place our troops and our partners at risk and jeopardise the fight against ISIL.”
There was no immediate claim of responsibility for the attack.
Iran-backed forces are deployed in close proximity to al-Tanf, a desert garrison on the strategically important Baghdad-Damascus highway, near the border with Iraq and Jordan.
Iran is a key ally of the Syrian government and the coalition has disrupted similar attacks on al-Tanf in the past.
Sleeper cells of the armed ISIL (ISIS) group are also active in the area.
The coalition set up the base in 2016 to train Syrian fighters for the war against ISIL.
It retained the facility even after the fighters’ last Syrian outpost was overrun by Kurdish-led forces in March 2019.
Roughly 900 US troops remain at al-Tanf and other bases in the Kurdish-controlled northeast as part of the coalition’s continuing campaign against ISIL remnants.
The US has previously carried out attacks targeting what it says were infrastructure facilities used by groups affiliated with Iran’s elite Revolutionary Guard Corps (IRGC).
The raids, it said, were in response to attacks allegedly launched by Iranian-backed fighters targeting al-Tanf.
The Syrian government has constantly expressed its opposition to the US role in Syria, and demanded that US forces withdraw.
