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 criticisms concern some members of the Parliamentary Assembly of the Council of Europe (PACE), accused of doing favours for Azerbaijan.
The oil-rich ex-Soviet state has cracked down on political dissidents.
There are suspicions that Azerbaijan influenced PACE's rejection of a report on Azeri political prisoners in 2013.
Azerbaijan is among the 47 member nations of the Strasbourg-based Council of Europe.
The council - not part of the EU - monitors compliance with the European Convention on Human Rights, and judges in Strasbourg enforce it.
In January 2013 PACE rejected a report by German Social Democrat MP Christoph Strässer, which deplored human rights abuses in Azerbaijan and urged the authorities there to release political prisoners.
The Azeri government denies that charges against opposition activists are politically motivated.
Opponents of President Ilham Aliyev have been jailed on various charges, including tax evasion, spying and weapons possession.
Three top international human rights lawyers will investigate the PACE corruption allegations and will report their findings by the end of 2017. They can recommend action against any PACE members implicated in corruption.
The investigators are:
PACE elects the judges at the ECHR, whose human rights rulings are binding on Council of Europe states.
As part of the inquiry, PACE plans to revise its code of conduct.
An investigation published in December by the European Stability Initiative (ESI), a human rights think-tank, alleged that some parliamentarians in PACE had engaged in political lobbying for Azerbaijan. There were claims that some received Azeri payments.
Council of Europe profile
Azerbaijan bans online insults to leader
In March a top Council of Europe official, Secretary General Thorbjorn Jagland, wrote to PACE President Pedro Agramunt, urging him "to establish an independent external investigation body without any further delay".
A large group of European MPs in PACE made a similar plea in January. They said PACE's integrity was threatened by "recent, serious and credible allegations of grave misconduct" by some fellow MPs.
Civil society groups in Europe sent an open letter to PACE in April, saying an independent investigation must "shed light on hidden practices that favour corruption".
The US military says it has carried out air strikes against the al-Qaeda-linked Khorasan group in north-western Syria.
[NEXT_CONCEPT]
Europe's top human rights watchdog, the Council of Europe, has launched an investigation into alleged corruption at the council involving Azerbaijan.