The US military, in a statement, said an air raid near Aleppo destroyed an IS ant-aircraft artillery piece and a jihadist fighting position.
"It's the first time that the international coalition has supported non-Kurdish opposition forces fighting the Islamic State," Observatory director Rami Abdel Rahman told AFP.
He said at least eight IS fighters were killed in the strikes and another 20 were injured.
Syria expert Thomas Pierret said the raids showed Washington was intent on preventing IS from expanding in Aleppo province, which is currently largely divided between regime and rebel control.
"Washington seems really determined to stop IS from advancing against the rebels in Aleppo," said Pierret, a professor at the University of Edinburgh.
The strikes showed Washington's "pragmatism", he said, noting that Al-Qaeda affiliate "Al-Nusra only constitutes a small part of the rebel forces that are fighting IS," in Aleppo, with moderate forces holding more territory.
Syrian state television said government forces launched air strikes near Suran on "terrorists", the term used by Damascus for all those fighting to oust President Bashar al-Assad.
It gave no further details.
IS captured Suran a week ago and has been fighting an alliance of rebels including Al-Nusra and Islamist Ahrar al-Sham in the surrounding area.
Both Al-Nusra and Ahrar al-Sham have been targeted in US-led raids and like IS, Al-Nusra is blacklisted as a "terrorist organisation" by Washington.
- 'America's spies' -
IS has been seeking to expand its territory by seizing the Aleppo towns of Marea and Azaz, which lie on key supply routes for rival rebels.
Online, IS supporters accused Al-Nusra and Ahrar al-Sham of collaborating with the US-led coalition, denouncing them as "America's spies" and collaborators with the "crusader coalition."
Despite sharing a jihadist ideology, Al-Nusra and IS are fierce rivals, with IS seeking to expand its self-declared "caliphate" in territory it holds in Syria and Iraq.
Al-Nusra pledges allegiance to Al-Qaeda chief Ayman al-Zawahiri, but has for now confined its ambitions to Syria and has allied with conservative Islamist groups fighting the regime and IS.
The US-led coalition began its air campaign in Syria last September but the majority of its strikes have been confined to areas where IS has undisputed control or is battling Kurdish forces.
Syria's conflict began in March 2011 with anti-government demonstrations but descended into a brutal war after a regime crackdown.
It has evolved into a complex battle with multiple fronts, and involving the regime, rebels, jihadists and Kurdish forces.
- IS repelled in Hasakeh -
On Sunday in northeastern Syria, the Observatory and Syrian state media said government troops had pushed IS fighters back from Hasakeh city after fierce fighting.
IS began an assault on the city, which is capital of the province of the same name, on May 30 and by Thursday advanced to the city's southern entrance.
But the Observatory said the jihadists had pulled back two kilometres after heavy fighting.
At least 119 people have been killed since the assault began, among them 71 regime forces and 48 IS fighters, 11 of them suicide bombers.
Syria's official SANA news agency also reported the fighting, saying the army had retaken several positions captured by IS in recent days, including an electricity station and a prison being used as a military base.
The Observatory said fighting was now continuing in the area near the prison.
Control of Hasakeh city is shared between government forces and Kurdish fighters, who did not initially enter into combat against IS.
But the Observatory said Kurdish forces began fighting IS on the outskirts of the areas under their control in the west of the city on Saturday night.
Syria's Kurds have walked a careful line in the country's conflict, declining to join the uprising directly, but also not fighting alongside the regime.
In Hasakeh, they share control of the city's security with regime forces, but the arrangement has been tense at times with occasional skirmishes breaking out.
Also on Sunday, the Observatory reported that 17 people were killed in three barrel bomb attacks launched by regime forces in the north of the central province of Homs.