The strike comes two days after an American outpost in southern Syria was attacked.
The US military has killed senior al-Qaeda leader Abdul Hamid al-Matar in a drone strike in Syria, a US Central Command spokesman said.
“The removal of this al-Qaeda senior leader will disrupt the terrorist organisation’s ability to further plot and carry out global attacks threatening US citizens, our partners, and innocent civilians,” US Army Major John Rigsbee said in a written statement late on Friday.
There were no other known casualties from the strike, he said, adding it was conducted using an MQ-9 aircraft.
The strike comes two days after a US outpost in southern Syria was attacked.
“Al-Qaeda continues to present a threat to America and our allies. Al-Qaeda uses Syria as a safe haven to rebuild, coordinate with external affiliates, and plan external operations,” Rigsbee said.
Rigsbee did not say if the US drone strike was carried out in retaliation for the attack. He also did not say which area of Syria the strike was conducted.
In September, the Pentagon also conducted a strike in rebel-controlled northwestern Syria, killing another senior al-Qaeda leader, Salim Abu-Ahmad.
The earlier airstrike was conducted near the governorate of Idlib.
Large parts of Idlib and neighbouring Aleppo remain in the hands of Syrian armed opposition, dominated by armed groups including the once al-Qaeda linked Hayat Tahrir al-Sham.
The ongoing war in Syria has created a complex battlefield involving foreign armies, militias and other armed groups linked to al-Qaeda, the Islamic State of Iraq and the Levant (ISIL, also known as ISIS) and other affiliated groups.
The war has killed around half a million people since starting in 2011 with a brutal crackdown on anti-government protests.