The 59-year-old Egyptian's death was reported by a number of experts on Syria and terrorism, including Charles Lister of the Middle East Institute.
Photos and video posted on social media suggested he was targeted by a drone as he travelled in a car on Sunday.
Pictures show a Kia car on the side of a road with a massive hole in its roof, with footage showing the difficult removal of a body from the vehicle's demolished interior.
Two people were said to have been killed in the drone attack in al-Mastouma in Syria's northern Idlib province.
Abu Khayr al-Masri, who was reportedly married to a daughter of Osama bin Laden, was allegedly responsible for a number of terror attacks, including the bombings of the US embassies in Kenya and Tanzania in 1998.
He was an Islamic militant in Egypt before fleeing the country in the 1980s, and fought in the Bosnian War in the 1990s before eventually making his way to Afghanistan.
He fled that country after the September 11 terror attacks in the US, eventually landing in Iran where he and other senior al-Qaeda members were arrested in 2003.
He travelled to Syria after he was released from custody in Iran in March 2015 along with two other al-Qaeda leaders.
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