The coalition said two allied Syrian opposition fighters were injured in the attack on al-Tanf, where US troops are stationed.
A drone strike hit a US-led coalition base in southern Syria, the US military’s Central Command said.
“Three disposable attack drones have struck the al-Tanf garrison in Syria,” a CENTCOM statement said Friday.
Two of the drones were shot down by the coalition, but the third struck the terrain, injuring two allied Syrian opposition fighters who were being treated, the statement added.
“Attacks of this nature are unacceptable,” said CENTCOM spokesman Joe Buccino, without specifying who carried out them.
“You are putting our troops and our partners at risk and jeopardizing the fight against ISIL.”
There was no immediate admission of responsibility for the attack.
Iran-backed forces are stationed in close proximity to al-Tanf, a desert garrison on the strategic Baghdad-Damascus highway, near the borders with Iraq and Jordan.
Iran is a key ally of the Syrian government, and the coalition has prevented similar attacks on al-Tanf in the past.
Sleeper cells from the armed group ISIL (ISIS) 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 last Syrian fighter outpost was overrun by Kurdish-led forces in March 2019.
Around 900 US troops remain in al-Tanf and other bases in the Kurdish-controlled northeast as part of the ongoing coalition campaign against what remains of ISIS.
The US has previously carried out attacks on alleged infrastructure facilities used by groups affiliated with Iran’s elite Revolutionary Guard Corps (IRGC).
The raids were in response to attacks allegedly launched by Iran-backed militants against al-Tanf.
The Syrian government has consistently opposed the US role in Syria and has called for the withdrawal of US forces.