 Bin Laden and al-Zawahiri, left, are on the top of the wanted list |
National Intelligence Director John Negroponte said al-Qaeda was strengthening its ties across the Middle East, North Africa and Europe.
Pakistan rejected the comments, which are the most specific on the issue yet.
This week, the US carried out air strikes in Somalia targeting what it believed to be members of al-Qaeda.
The BBC's James Westhead in Washington says that until now the US has not been so specific about where it believes al-Qaeda's leaders are hiding.
Such a claim will be embarrassing for Pakistani President Pervez Musharraf, who Mr Negroponte described as a key partner in America's war on terror, our correspondent says.
Afghanistan has welcomed the comments. President Hamid Karzai's chief-of-staff, Jawed Ludin, told the BBC that Afghanistan had long maintained that the Islamic militants operated from within Pakistan, and that Mr Negroponte's statement was refreshing in its honesty.
'Secure hide-out'
Mr Negroponte told a Senate committee that al-Qaeda was still the militant organisation that "poses the greatest threat to US interests".
"They are cultivating stronger operational connections and relationships that radiate outward from their leaders' secure hideout in Pakistan to affiliates throughout the Middle East, North Africa and Europe," he said.
"We have captured or killed numerous senior al-Qaeda operatives, but al-Qaeda's core elements are resilient. They continue to plot attacks against our homeland and other targets with the objective of inflicting mass casualties," Mr Negroponte added. 
He did not say where in Pakistan the group's leadership was hiding, or refer to its chief, Osama Bin Laden, or his second-in-command, Ayman al-Zawahiri, who are wanted for masterminding the 11 September attacks on Washington and New York.
New job
But the unusually forthright statement by Mr Negroponte appears to be the first time the US has publicly singled out Pakistan, one of its key allies, as the current home of al-Qaeda's high command.
Previously, officials had spoken more vaguely about the group having bases in the mountainous border area between Pakistan and Afghanistan.
"Pakistan is our partner in the war on terror and has captured several al-Qaeda leaders. However, it is also a major source of Islamic extremism," Mr Negroponte said in written testimony submitted to the Senate committee. 
Pakistani foreign office spokeswoman Tasneem Aslam rejected the comments.
"Pakistan does not provide a secure hideout to al-Qaeda or any terrorist group," she said. "In fact the only country that has been instrumental in breaking the back of al-Qaeda is Pakistan."
Pakistani Interior Minister Aftab Sherpao also played down Mr Negroponte's comments as "too general", saying that Pakistan responded to specific information about al-Qaeda members and claiming that the movement was totally marginalised.
Difficult border
The head of the US Defence Intelligence Agency, Lt-Gen Michael Maples, said Pakistan's border with Afghanistan remained a haven for al-Qaeda and other militants.
The tribal areas on the border are thought to be where al-Qaeda leader Bin Laden and his deputy Zawahiri could be hiding.
Pakistan and Afghanistan share a 1,400-mile (2,250km) mountainous border which is extremely difficult to patrol.
Taleban and al-Qaeda fighters are thought to be operating on both sides.
The two countries regularly exchange charge and counter-charge over who is to blame for the violence.
Recently, Pakistan reiterated its intention to fence and mine sections of the troubled border.
Kabul particularly opposes the idea of mining stretches of the frontier, saying it will endanger civilian lives.
An Islamist insurgency spearheaded by the resurgent Taleban militia is at its strongest in the southern Afghan provinces bordering Pakistan.
Mr Negroponte took charge of the 16 US intelligence agencies in April 2005, but is shortly due to move to the state department where he will become Condoleezza Rice's deputy.
President George W Bush last week named retired Navy Vice Admiral Michael McConnell as the new US national intelligence director.
Mr Negroponte made the claims about Pakistan in his annual assessment of worldwide threats against the US and its interests.
