A restaurant in northern Syria's Manbij town center was rocked by an explosion Wednesday, killing at least 16 people and injuring many others, a Syrian war monitoring group said.
The Britain-based Syrian Observatory for Human Rights (SOHR) said the blast occurred near a patrol of the U.S.-led coalition.
The attack killed two U.S. soldiers, one Department of Defense civilian and a contractor, the Pentagon confirmed hours after the explosion.
Three others wounded in the blast, a U.S. official told Reuters.
The dead included nine civilians and at least five PKK-linked People's Protection Forces (YPG) terrorists, according to the SOHR.
The monitor said the blast was likely set off by a suicide bomber.
The U.S.-led coalition said that "U.S. service members were killed during an explosion while conducting a routine patrol in Syria today."
Videos released by local activists and news agencies showed a restaurant that suffered extensive damage and a street covered with debris and blood. Several cars were also damaged. Other videos showed helicopters flying over the area reportedly to pick up victims.
Daesh terrorist group later claimed responsibility for the attack that hit U.S.-led forces.
"A suicide attack carried out with explosives vest hit an international coalition patrol in the city of Manbij," the terror group's propaganda arm Amaq said.
The attack comes as the U.S. has begun the process of withdrawing from Syria.
In initial remarks from the U.S. administration, Vice President Mike Pence said the United States would fight to ensure the defeat of the Daesh but reiterated plans to pull troops out of Syria.
"We'll stay in the region and we'll stay in the fight to ensure that ISIS does not rear its ugly head again," Pence told a gathering in Washington of U.S. ambassadors stationed around the world using an alternate acronym for the terrorist group.
Speaking at a joint press conference with his Croatian counterpart Kolinda Grabar-Kitarović in Ankara, Turkish President Recep Tayyip Erdoğan said that the recent information provided to him shows that five American soldiers have been killed in the attack, with the total death toll standing at 20.
"The attack in Manbij might have been meant to affect Trump's decision to pull out from Syria. But as I saw Mr. Trump's decisiveness, I don't think a backward step would follow such a terror attack. Otherwise, it would mean a victory for Daesh," he added.
The Turkish Ministry of Foreign Affairs released a statement later in the day, condemning the attack. "We condemn the heinous terror attack in Syria's Manbij," the statement said.
The town and its surrounding area has been controlled by the U.S.-backed Syrian Democratic Forces (SDF), which is dominated by the YPG terrorist group, since Aug. 2016 after ousting Deash terrorists who captured the town from moderate opposition in Jan. 2014.
Manbij is one of the two areas controlled by the SDF/YPG on the right bank of the Euphrates River, with the other being the area including the town of Tabqah in central Syria.
Turkey strongly opposes YPG's presence in Manbij and reached a deal with the U.S. in June to end the terrorist group's presence in the town and conduct joint patrols.
It was not the first time that forces of the U.S.-led coalition were subjected to attacks in the area, although they have been rare.
In March last year, a roadside bomb killed two coalition personnel, an American and a Briton, and wounded five in Manbij.