The US hit five targets related to the group, including several vehicles and buildings, near the border with Turkey.
The UK-based Syrian Observatory for Human Rights, which monitors the violence, said several militants and two children had died in the attack.
It is the second time US strikes have targeted Khorasan, whom it accuses of planning attacks on the US and Europe.
In a statement, the US Central Command (Centcom) said Thursday's strikes near the town of Sarmada had hit vehicles and buildings used for training and to produce explosive devices.
A senior US official, who spoke on condition of anonymity, told reporters that one of the targets was a French militant called David Drugeon, who had joined the group.
The official said it was unclear as to whether he had been killed in the strikes, but added: "We think we got him."
Little is known about Khorasan other than information released by US officials.
They say the group is made up of veteran fighters from the Afghanistan and Pakistan region who have embedded within al-Qaeda's Syria branch, the al-Nusra Front.
Centcom said the group was using Syria as a base to attack the West, rather than seeking to overthrow Syrian President Bashar al-Assad or helping the Syrian people.
The first strikes on the group were on 23 September during the US-led coalition's first raids against Islamic State (IS) fighters in Syria.
At the time, Pentagon's operations chief Lt Gen William Mayville said Khorasan militants were in "the final stages of plans to execute major attacks".
The US-led coalition has launched several air strikes in Syria since September, mostly targeting IS fighters.
Syria's civil war, which is in its fourth year, has claimed more than 200,000 lives.
President Assad's government has been battling against an armed and increasingly fragmented uprising.
As well as fighting the government, rebel groups such as the Nusra Front and IS have also been fighting among themselves.
The US military says it has carried out air strikes against the al-Qaeda-linked Khorasan group in north-western Syria.