A US drone strike has killed al-Qaeda's second-in-command, in a significant blow to the terrorist network that has lost a string of top leaders since the death of Osama bin Laden last year.

Abu Yahya al-Libi was considered a media-savvy, charismatic leader who escaped from an American prison in Afghanistan and helped preside over the transformation of al-Qaeda into a terrorist movement aimed at winning converts around the world.

Al-Libi was the latest in the dozen-plus senior commanders removed in the clandestine US war against al-Qaeda since Navy SEALs killed bin Laden.

An American official who confirmed al-Libi's death said no one left in al-Qaeda comes close to replacing the expertise the group has just lost.

Al-Libi was killed on Monday morning.

Pakistani officials had previously said that eight militants died in a drone strike in the Pakistani village of Khassu Khel in the North Waziristan tribal area.

Al-Libi, a hero in militant circles for his 2005 escape from an American military prison in Afghanistan, was elevated to al-Qaeda's No.2 spot when Ayman al-Zawahri rose to replace bin Laden shortly after the terrorist leader was killed on May 2, 2011.

The State Department's Rewards for Justice program had set a $US1 million reward for information leading to al-Libi, who had filmed numerous propaganda videos urging attacks on US targets.

Militants and residents in the area told Pakistani agents that al-Libi was in a house when it was hit, Pakistani intelligence officials said. They said the mud and brick house was destroyed in the attack. A vehicle used by al-Libi was destroyed during the strike.

The US has carried out a flurry of drone strikes recently - seven in less than two weeks - some of which appear to have been trying to target al-Libi. The al-Qaeda deputy appeared to have been injured in one of those strikes, although there were conflicting accounts as to which.