The official said the strikes were in self-defense after the pro-government forces began firing artillery and tank rounds at the US-backed Syrian Democratic Forces. About 100 of the attackers were killed, the official said.
It was a rare US strike against forces that support Syrian President Bashar Assad's regime.
The official said the pro-regime troops were in a large formation supported by artillery, tanks, multiple-launch rocket systems and mortars, and that 20 to 30 artillery and tank rounds landed within some 550 yards (500 meters) of the SDF headquarters.
Several US officials said no Americans were injured or killed in the attack by the pro-regime forces, but one SDF member was wounded. All officials spoke on condition of anonymity to discuss preliminary details of the attack.
In response to the attack, officials said the Syrian Democratic Forces supported by the coalition targeted the pro-government troops with a combination of airstrikes and artillery rounds. Any of the attacking vehicles and personnel who turned around and headed back west were not targeted, the military official said.
The SDF, aided by coalition support, are battling Islamic State militants east of the Euphrates River. Syrian government forces are active on the other side of the river around the city of Deir el-Zour.
The military official said the coalition had been observing a slow buildup of pro-government forces over the past week, and alerted Russian officials of the SDF presence in Khusham. Coalition officials were in regular communication with Russian counterparts before, during and after the attack, the official said, and Russian officials assured coalition officials they would not strike coalition forces in the vicinity.
Officials said it appeared that the pro-regime forces were trying to take back land that the SDF had liberated from IS fighters last September, including oil fields in Khusham.