Six civilians, including a child, were among at least 22 people killed in US air strikes on the Islamic State group's de facto Syrian capital on Saturday and Sunday, a monitor said.
The rest of the dead in the raids on the city of Raqa were IS fighters, the Syrian Observatory for Human Rights said.
Dozens of people were also wounded.
The US-led coalition, which launched an air war against IS in Syria last September, said it had carried out "significant" air strikes against Raqa.
"The significant air strikes tonight were executed to deny Daesh (IS) the ability to move military capabilities throughout Syria and into Iraq," spokesman Lieutenant Colonel Thomas Gilleran said.
"This was one of the largest deliberate engagements we have conducted to date in Syria and it will have debilitating effects on Daesh's ability to move from Raqa."
Coalition forces "successfully engaged multiple targets" throughout Raqa, the statement said, destroying IS structures and transit routes.
The strikes "have severely constricted terrorist freedom of movement," it added.
Washington is leading a coalition fighting IS in Syria and Iraq, where the extremist group has proclaimed an Islamic "caliphate" in territory under its control.
The group emerged in Syria in 2013, and now controls around half the country's territory, though much of the land it holds is unpopulated desert.
More than 230,000 people have been killed in Syria since the conflict began in March 2011.