Zahran Alloush, head of the powerful Jaish al-Islam Syrian rebel group, was killed on Friday east of Damascus, a monitoring group and Syria's opposition said, according to AFP.
His death "stands as one of the most significant opposition losses" of Syria's nearly five-year uprising, analyst Charles Lister said on Twitter.
The Syrian Observatory for Human Rights monitor said Alloush and five other commanders were killed "in an air strike that targeted one of their meetings in Eastern Ghouta."
The death of Alloush, 44, was confirmed on Twitter by the head of Syria's opposition National Coalition, who posted a message of condolence.
Syria's state television channel also reported the death by air strike, but did not say who had carried out the raid.
Jaish al-Islam is the most prominent rebel faction in the Eastern Ghouta region, an opposition bastion east of the capital, and was recently represented at landmark opposition talks in Saudi Arabia.
Members of the group have been accused of using dozens of captives in metal cages as "human shields" in an attempt to prevent regime bombardment.
The group’s stronghold in Eastern Ghouta is under regular bombardment of the regime. Air raids on Thursday by Syrian government warplanes in the region killed at least 28 civilians, including 10 children, and wounded at least 60 others.
Alloush's death comes after Syria's army announced a massive operation to retake rebel-held Eastern Ghouta. The regime's forces have been backed by Russian air strikes since September 30.
Jaish al-Islam was known to have extremist views and to have supported the establishment of an Islamic state before recently moving towards a more moderate position. The group was among the signatories of a statement denouncing the November 13 Paris attacks committed by the Islamic State (ISIS).
Alloush spent at least two years in Syrian prisons before being released in a general amnesty in June 2011.
(Arutz Sheva’s North American desk is keeping you updated until the start of Shabbat in New York. The time posted automatically on all Arutz Sheva articles, however, is Israeli time.)