The US-led coalition fighting ISIS militants said troops opened fire on Wednesday at a checkpoint in northeast Syria after they came under small arms fire.
A Syrian was killed and another wounded in the rare clash between American troops and a group of government supporters.
The coalition said in a statement that the situation had calmed down and the patrol had returned to the base.
"After coalition troops issued a series of warnings and de-escalation attempts, the patrol came under small arms fire from unknown individuals," said Col Myles Caggins, a spokesman for the US-led coalition.
"In self-defence, coalition troops returned fire," he said.
He said one US soldier had "a minor superficial scratch while operating their equipment" and was back at work.
The state-run media said the killed man was a civilian. He was among residents of a village east of the town of Qamishli who had gathered at an army checkpoint, pelting the US convoy with stones and taking down a US flag from one of the vehicles. At that point, American troops fired with live ammunition and smoke bombs at the residents, the reports said.
A US military spokesman said coalition forces conducting a patrol near Qamishli encountered a checkpoint occupied by pro-Syrian government forces. The patrol came under small-arms fire from unknown individuals after coalition troops issued the series of warnings in an attempt to de-escalate the situation, said Col Caggins.
Air Force Lt Col Carla Gleason, travelling with the US defence secretary in Brussels, said no Americans were killed in the incident.
Hundreds of US troops are stationed in north-east Syria, working with their local partners from the Kurdish-led Syrian Democratic Forces to fight against ISIS. The US carries out patrols in north-east Syria, but it was not immediately clear why the convoy drove into a government-controlled area.
The incident marks a rare confrontation involving US and Syrian troops in the crowded region where Russian forces are also deployed – and is certain to further escalate tensions.
State-run Al-Ikhbariya TV aired a cellphone video showing an armoured vehicle flying a US flag standing on a rural road while a car appeared to be blocking its way.
Locals are seen walking past the US armoured vehicle, with at least two soldiers inside, one of whom steps down as civilians approach. One civilian is seen tearing a US flag as he approaches the soldier.
The TV said protests spread, preventing reinforcements from coming to help the US convoy. The report said the wounded civilian and was being treated at the Qamishli hospital.
The Syrian Observatory for Human Rights said residents and armed pro-government militiamen in Khirbet Ammu blocked the path of a US convoy. The militia fired in the air, prompting the American troops to fire smoke bombs. Tension escalated and US troops killed one person, the Observatory said.
The Observatory, which has a network of activists on the ground, said it is not clear if the killed was a civilian or a militia member. The Observatory also said that a Russian convoy arrived on the scene to defuse the tension.
The Syrian war, now in its ninth year, has pulled in international players including the US, Russia and Turkey. Russia has supported President Bashar Al Assad’s government, while Turkey is the rebels’ main backer.