The Britain-based Syrian Observatory for Human Rights said the blast occurred near a patrol of the U.S.-led coalition.
Seven people, including one U.S. serviceman and six civilians, were killed in the explosion, the Observatory said.
The monitor said the blast was likely set off by a suicide bomber.
Daesh 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 said.
The attack comes as the U.S. has begun the process of withdrawing from Syria.