Anwar al-Awlaki was killed in a strike on his convoy carried out by a joint operation of the CIA and the U.S. Joint Special Operations Command, according to counterterrorism officials, speaking on condition of anonymity to discuss intelligence.
Analysts said he is the most prominent al Qaeda figure to be killed since Osama bin Laden.
Yemen's Defense Ministry also said another American in al Qaeda, Samir Khan, was killed with al-Awlaki. He was the editor of al Qaeda's propaganda magazine "Inspire."
Late Friday, the Associated Press quoted sources that al Qaeda's chief bomb maker in Yemen, Ibrahim al-Asiri, was also killed. The F.B.I. pulled al-Asiri's fingerprints on the explosives worn by the underwear bomber.
According to some experts, al-Asiri was so important to the organization that his death would overshadow the news of al-Awlaki and Khan.
A U.S. official said that a total of four individuals were killed in the attack.
Authorities say al-Awlaki had been under observation for three weeks while the military waited for the right opportunity to strike.
Officials say al-Awlaki was killed in a strike on his convoy carried out by a joint operation of the CIA and the U.S. Joint Special Operations Command.
A U .S. official said al-Awlaki inspired Maj. Nidal Hassan, the army major accused of killing 13 soldiers at Fort Hood in 2009.
Al-Awlaki is suspected of specifically organizing the failed underwear bomber attack on board a plane over Detroit that same year. The official also said Awlaki has sought to use poisons, including cyanide and ricin, to attack Westerners.
Al-Awlaki also is believed to have had a hand in mail bombs addressed to Chicago-area synagogues, packages intercepted in Dubai and Europe in October 2010.
Al-Awlaki's death is the latest in a run of high-profile kills for the U.S. under President Barack Obama. But the killing raises questions that the death of other al-Qaida leaders, including bin Laden, did not.
Al-Awlaki was a U.S. citizen, born in New Mexico to Yemeni parents. Civil liberties groups have questioned the government's authority to kill an American without trial.
Republican presidential candidate Ron Paul condemned the Obama administration for the killing.
Paul, a Texas congressman known for libertarian views, said the killing of Anwar al-Awlaki on Yemeni soil amounts to an "assassination." Paul warned the American people not to casually accept such violence against U.S. citizens, even those with strong ties to terrorism.
Paul made the comments to reporters after a campaign stop Friday at Saint Anselm College in New Hampshire. He said America's leaders must think hard about "assassinating American citizens without charges."
President Barack Obama declared al-Awlaki's killing a "major blow" to al Qaeda.
Obama praised Yemen's government and security forces for its close cooperation with the U.S. in fighting al Qaeda in the Arabian Peninsula, arguably the terror network's most dangerous affiliate. With al-Awlaki's death, Obama said the affiliate remains "a dangerous but weakened terrorist organization."
The Associated Press contributed to this report.