Already struggling with the rise of rival jihadists from the Islamic State group, al-Qaeda has suffered a series of setbacks in recent months with several commanders reported killed.
In a video statement, al-Qaeda in the Arabian Peninsula (AQAP) confirmed that Nasir al-Wuhayshi was dead.
Wuhayshi "was killed in a US drone attack that targeted him along with two other mujahedeen," who were also killed, said the statement read by prominent al-Qaeda militant Khaled Omar Batarfi and dated June 15.
US officials were earlier reported to have been reviewing intelligence to confirm that Wuhayshi was killed in a CIA drone strike on June 9.
A local Yemeni official had told AFP that Wuhayshi was believed to have been killed in the raid in al-Qaeda-held Mukalla, in southeastern Yemen.
Another Yemeni official told AFP last week that a drone had fired four missiles at three al-Qaeda militants, including an unnamed "leading figure", near Mukalla port, killing them on the spot.
A former aide to bin Laden, Wuhayshi attended the group's al-Farouk training camp in Afghanistan in the late 1990s.
He is said to have fled Afghanistan in 2002 to Iran, where he was arrested and handed over to Yemen.
He was held there without charge until he escaped by tunnelling his way out of prison with 22 others in February 2006.
In 2007, Wuhayshi was named head of AQAP, which Washington considers al-Qaeda's deadliest branch.
When Bin Laden was killed by US commandos in Pakistan in May 2011, Wuhayshi warned Washington not to fool itself that it spelt al-Qaeda's demise.
