Two US troops and an interpreter were killed in central Syria after an alleged member of the Islamic State group opened fire on a joint US-Syrian patrol, officials said.
US Central Command (CENTCOM) announced the deaths on X after Syria's state media earlier reported that an attack in the city of Palmyra had wounded US and Syrian troops.
"An ambush by a lone ISIS gunman" resulted in the deaths and injuries to three additional troops, said CENTCOM, which oversees the US military in the Middle East.
"The gunman was engaged and killed," it said.
Pentagon spokesman Sean Parnell said the attack occurred as the soldiers "were conducting a key leader engagement" in support of counter-terrorism operations, while US envoy to Syria Tom Barrack said the ambush targeted "a joint US-Syrian government patrol".
"The savage who perpetrated this attack was killed by partner forces," US Defense Secretary Pete Hegseth wrote on X.
In a post on his Truth Social platform, US President Donald Trump vowed "very serious retaliation" mourning the loss of "three great patriots".
He described the incident in remarks to reporters as a "terrible" attack.
Mr Parnell said the identities of the dead troops would be withheld until after their families were notified.
The incident is the first of its kind reported since Islamist-led forces overthrew longtime Syrian ruler Bashar al-Assad in December last year, and rekindled the country's ties with the United States.
A Pentagon official, speaking on the condition of anonymity, said the attack "took place in an area where the Syrian President does not have control".
Syrian state news agency SANA, quoting a security source, earlier reported that several US troops and two Syrian service members had been wounded in the attack.
The soldiers were taking part in a "joint field tour" in Palmyra, which was once under the control of the Islamic State (IS) group, SANA reported.
A Syrian military official who requested anonymity said that the shots were fired "during a meeting between Syrian and American officers" at a Syrian base in Palmyra.
A witness, who asked to remain anonymous, said he heard the shots coming from inside the base.
According to the Syrian Observatory for Human Rights monitor, which has a wide network of sources inside Syria, the meeting came as part of an "American strategy to strengthen its presence and foothold in the Syrian desert".
Helicopters evacuated the wounded to the Al-Tanf base in southern Syria, where American troops are deployed, SANA said.
Last month, during Syrian President Ahmed al-Sharaa's visit to Washington, Damascus formally joined the US-led global coalition against the IS group.
US forces are deployed in Syria's Kurdish-controlled northeast as well as at Al-Tanf near the border with Jordan.
