SDF forces responded with artillery and called in U.S. air strikes.
US F-22 stealth jets, F-15 fighters, and MQ-9 drones were involved in the counterattack according to US Air Forces Central Command.
The combination of air and artillery strikes came after pro-regime troops attacked the compound of the Syrian Democratic Forces.
No U.S. -led coalition forces were injured in the attack, but one SDF member was wounded.
The coalition said the attack took place in Khusham in the Middle Euphrates River Valley, five miles east of the agreed-on "de-confliction" line created to separate Russian-backed regime troops and US-backed forces in Syria. Initial media reports, citing unnamed U.S. officials, suggested that some 100 Syrian soldiers had died in the assault by the coalition forces.
Some US forces are embedded with the SDF but they suffered no casualties.
Although Turkey has backed opposition troops since the Syrian conflict began in 2011, Ankara has moved closer to Assad's ally, Moscow. The head of the Britain-based monitoring group, Rami Abdel Rahman, said the aim of the attack appeared to be the capture of a key oil field and a major gas plant in an SDF-held area. The official says about 100 of the attackers were killed.
White added that all pro-government vehicles and personnel who turned around and headed west were not targeted during the coalition strikes.
"We appreciate the Russian Federation's professionalism and regular communication [with its military units deployed to Syria] via the de-confliction line", he noted.
Mattis described the attack on the US-backed fighters, who were accompanied by United States special operations forces, as "perplexing" but he said the retaliatory US-led coalition strikes were defensive and limited in nature.
"Syrian pro-regime forces initiated an unprovoked attack against well-established Syrian Democratic Forces headquarters February 7", the statement reads.
The rare strikes against pro-regime forces were confirmed by the US-led coalition Operation Inherent Resolve, which is in the region targeting Islamic State. The Syrian army is supported by Iranian-backed militias, Lebanese resistance Shitte group Hezbollah and Russian forces and contractors.
The latest US air strikes came more than two weeks after USA jets killed as many as 150 ISIS fighters in eastern Syria. Now that the common goal of clearing out IS militants from Syria is nearly realized, Damascus and its allies have repeatedly threatened war against US troops if they don't leave the country.
In June a year ago, a U.S. Navy jet shot down a Syrian plane after it attacked U.S. -backed fighters on the ground.
The pro-regime forces includes several hundred soldiers as well.
In May, coalition aircraft strike a pro-regime convoy as it approaches a training garrison near the Al-Tanf border crossing to Jordan.