The Syrian Observatory for Human Rights monitoring group and a militia source said two Americans were among the dead, but Reuters was unable to independently confirm the death toll. The coalition said in a tweet it was still gathering information.
An Islamic State-affiliated web site, Amaq, said a suicide attacker with an explosive vest had targeted a foreign military patrol.
Last month, U.S. President Donald Trump made a surprise announcement that he would withdraw all 2,000 U.S. troops from Syria after concluding Islamic State had been defeated there.
The announcement rattled allies in the region and top U.S. officials, including Secretary of Defense Jim Mattis who quit.
The coalition, in its tweet, said its forces had conducted "a routine patrol in Syria" on Wednesday.
Two witnesses described Wednesday's blast to Reuters. "An explosion hit near a restaurant, targeting the Americans, and there were some forces for the Manbij Military Council with them," one said.
The Manbij Military Council militia has controlled the town since U.S.-backed Kurdish-led forces took it from Islamic State in 2016. It is located near areas held by Russian-backed Syrian government forces and by anti-Assad fighters backed by Turkey.
One of the witnesses said there was a "heavy" presence of military aircraft over Manbij following the blast, which took place near a vegetable market.
Photographs on a local Kurdish news site, which Reuters could not verify, showed two mutilated bodies, several other bodies lying on the ground with people gathered around them, damage to a building and vehicles, and blood smears on a wall. (Reporting By Angus McDowall and Ellen Francis; Editing by Peter Graff)