US officials said on Tuesday that the Libyan-born al-Libi had recently been considered by US counterterrorism experts as the No 2 in the core al-Qaeda group led by Ayman al-Zawahiri.
It is difficult to independently confirm the reports of al-Libi's death. However, if the US claims are true, then al-Libi would be the latest of more than a dozen high-ranking al-Qaeda commanders killed during the past year.
The US state department had set a $1m reward for information leading to al-Libi.
US and Pakistan sources said on Monday that al-Libi was the target of a deadly drone attack in Pakistan's North Waziristan region. However, the US sources could not confirm whether he was killed in that raid.
Zawahiri has headed the group since al-Qaeda's founder, Osama bin Laden, was killed last year in a US commando raid on his hideout in Pakistan.
'Al-Libi still alive'
A US official described al-Libi as "among al-Qaeda's most experienced and versatile leaders", saying that he "played a critical role in the group's planning against the West, providing oversight of the external operations efforts".
The drone raid that targeted al-Libi killed 15 people, according to Pakistani officials, who said more than half of the victims were "foreigners", most of them Arabs.
It was the third drone attack in as many days in Pakistan's tribal regions. A bombing on Saturday killed four people, and another on Sunday killed 10 more.
The Pakistani foreign ministry summoned Richard Hoagland, the US charge d'affaires in Islamabad, on Tuesday to convey the "government's serious concern regarding drone strikes in Pakistani territory".
Unidentified leaders in Taliban Pakistan have said that al-Libi is alive, and that he was not in his car when it was targeted. His driver and bodyguard were killed in the drone strike.
"This is not the first time claims have been made about his death. The Americans are suffering heavy losses in Afghanistan so they have resorted to making false claims," a commander in North Waziristan closely associated with foreign fighters told Reuters news agency.
Bagram base detainee
Al-Libi reportedly travelled to Afghanistan in the 1990s. He was captured in 2002 and detained at Bagram airbase in Afghanistan.
But he escaped in 2005, along with three other detainees, and was never recaptured. He is the only one of the four still at large; the rest have either been captured or killed.
Al-Libi was elevated to al-Qaeda's number-two position last year, after the US raid in Pakistan which killed Osama bin Laden.
He was not considered a skilled military commander - his value to the group was mostly as a propagandist. He appeared frequently in the group's recruitment videos.
This is not the first time the US has reported him dead: al-Libi was initially believed to be the target of a drone attack in December 2009, but the actual victim was Saleh al-Somali, dubbed al-Qaeda's "external operations" chief.
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