US officials painted the 59-year-old long-time number two as an "armchair general" with no combat experience, saying he not only lacked charisma and leadership skills but was also a divisive figure who could fracture Al-Qaeda.
Top US military officer Admiral Mike Mullen told Zawahiri to expect the same treatment meted out to bin Laden, who was killed by US commandos in the dead of night in a May 2 raid on his hideout in Pakistan.
"As we did both seek to capture and kill -- and succeed in killing -- bin Laden, we certainly will do the same thing with Zawahiri," said Mullen, who is chairman of the Joint Chiefs of Staff.
US Defense Secretary Robert Gates, giving his valedictory press briefing at the Pentagon, could barely disguise his scorn, but warned that the announcement should serve as a reminder of the continuing Al-Qaeda threat.
"First of all I think we should be mindful that this announcement by Al-Qaeda reminds us that despite having suffered a huge loss... Al-Qaeda seeks to perpetuate itself, seeks to find replacements for those who have been killed, and remains committed to the agenda that bin Laden put before them."
But Gates, who joked that it was "probably tough to count votes when you're in a cave," said Zawahiri faced "some challenges."
"Bin Laden has been the leader of Al-Qaeda essentially since its inception," he said. "In that particular context he had a peculiar charisma that I think Zawahiri does not have. I think he was much more operationally engaged than we have the sense Zawahiri has been."
Gates also alluded to possible suspicion within Al-Qaeda because of Zawahiri's Egyptian nationality, a point taken up earlier by a senior administration official.
"He hasn't demonstrated strong leadership or organizational skills during his time in AQ (Al-Qaeda) or previously while in the Egyptian Islamic Jihad," the official said, asking to remain anonymous.
"His ascension to the top leadership spot will likely generate criticism if not alienation and dissension with Al-Qaeda."
The official stressed that Zawahiri had not had any actual combat experience, and had opted instead "to be an armchair general with a 'soft' image."
"The bottom line is that Zawahiri has nowhere near the credentials that (bin Laden) had," he added.
"No matter who is in charge, he will have a difficult time leading AQ while focusing on his own survival as the group continues to hemorrhage key members responsible for planning and training operatives for terrorist attacks."
Like his slain Saudi-born co-conspirator, Zawahiri has been in hiding since the United States declared its war on terror after the September 11, 2001 attacks.
Now Washington's most wanted man, Zawahiri was jailed for three years in Egypt for militancy and was implicated in the assassination of Egyptian president Anwar Sadat in 1981, and a 1997 massacre of tourists in Luxor.
Facing a death sentence, Zawahiri left Egypt in the mid-1980s initially for Saudi Arabia, but soon headed for Pakistan's northwestern city of Peshawar where the resistance to the Soviet occupation of Afghanistan was based, and then to Afghanistan, where he joined forces with bin Laden.
