The strike by the coalition fighting the Islamic State group happened on the same day IS jihadists killed more than 50 people in attacks on two government-held villages elsewhere in the country.
It came as the United Nations said Syria's regime and rebels had agreed to set up expert committees to discuss "constitutional issues" at the latest round of UN-backed peace talks in Geneva.
US-led aircraft struck the convoy as it headed toward a remote coalition garrison near the border with Jordan, a US defence official said.
"Then there was finally a strike against the lead portion of that movement."
The coalition said the strike had occurred "well inside" an established de-confliction zone northwest of the Al-Tanaf garrison, where British and US commandos have been training and advising local forces fighting IS.
Pentagon chief Jim Mattis said, despite the strikes, the United States was "not increasing our role in the Syrian civil war, but we will defend our troops".
The United States has been militarily involved in Syria since 2014, but has for the most part avoided engaging directly in the conflict.
But last month, it launched a barrage of missiles at Syria's Shayrat airbase, which it said was the launchpad for an alleged chemical attack that killed dozens of civilians.
Also yesterday, IS killed more than 50 people in an attack on two regime-held villages in the central province of Hama, said the Observatory.
The attack on the villages of Aqareb and Al-Mabujeh killed at least 15 civilians and 27 pro-government fighters, it said.
IS also lost 15 fighters in the dawn attack on the villages in the east of the province, said the monitor.
Observatory director Rami Abdel Rahman said at least three of the civilians were killed execution style with knives, a man and his two children.
State media also reported 52 people had been killed in the IS assault, though it described the attack as against Aqareb only.
It said IS fighters had mutilated the bodies of villagers and looted their homes, and said 15 of the dead were children.
The Observatory said IS had seized control of Aqareb and part of Al-Mabujeh in the attack, which began with heavy shelling on a nearby regime checkpoint.
IS has attacked Al-Mabujeh before with devastating effect.
In March 2015, it executed at least 37 civilians in the village, whose population includes Sunnis as well as those from the Ismaili sect and the Alawite community to which President Bashar al-Assad belongs.
During the same assault the group kidnapped at least 50 civilians, half of them women.
Control of Hama province is divided between the government, rebel forces and IS, which is present mostly in the east of the area.
IS faces pressure in northern Syria, where an alliance of Kurdish and Arab fighters is preparing an assault on its bastion Raqa city.
Disclaimer: No Business Standard Journalist was involved in creation of this content
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