The statement was very light on details, but accused pro-Syrian forces of attacking the "headquarters" of the Syrian Defense Forces, where USA troops were stationed.
No American troops were killed or wounded in the incident, officials said.
No U.S. casualties were reported after the confrontation.
Officials say the airstrikes were in defense "of coalition and partner forces".
Syrian government forces are active on the other side of the river around the city of Deir al-Zor.
The strikes came after the pro-regime militants initiated an attack against the headquarters of the Syrian Democratic Forces (SDF).
The operation was launched after "20 to 30 artillery and tank rounds landed within 500 meters of the SDF headquarters location".
At least 100 militants were killed in the Coalition's attack, a USA military official told reporters on Wednesday.
After the attack the coalition "conducted strikes against attacking forces to repel the act of aggression".
USA officials said no Americans were injured or killed in the attack by the pro-regime forces.
More than 100 fighters aligned with Syrian President Bashar Al-Assad were killed in the attack last night and in the early hours of this morning, a USA official said.
The U.S. maintains about 2,000 troops in the country.
Skirmishes between the SDF and Syrian Regime Forces are not uncommon given the recent major defeats of ISIS, with the retaking of its former capital Raqqa last October, resulting in both armed group's advances connecting. The official said they have not ruled out that Iranian backed-forces might have also been involved in the attack.
Neither was it clear whether Russian Federation, which is conducting its own air campaign in support of the Syrian government, may have had any role in the incident.