When asked about the use of drones by his administration in a chat with web users on Google+ and YouTube, Obama said "a lot of these strikes have been in the Fata" - Pakistan's Federally Administered Tribal Areas.
"For the most part, they've been very precise precision strikes against al-Qaeda and their affiliates, and we're very careful in terms of how it's been applied," Obama said.
"This is a targeted focused effort at people who are on a list of active terrorists, who are trying to go in and harm Americans, hit American facilities, American bases, and so on."
Explaining that many strikes were carried out "on al-Qaeda operatives in places where the capacities of that military in that country may not be able to get them", Obama confirmed that Pakistan's lawless tribal zone was a target.
"So, obviously, a lot of these strikes have been in the Fata, and going after al-Qaeda suspects who are up in very tough terrain along the border between Afghanistan and Pakistan," he said.
Sanctuary for terrorism
"For us to be able to get them in another way would involve probably a lot more intrusive military action than the ones we're already engaging in."
US officials say Pakistan's tribal belt provides sanctuary to Taliban fighting for 10 years in Afghanistan, al-Qaeda groups plotting attacks on the West, Pakistani Taliban who routinely bomb Pakistan and other foreign fighters.
Sixty-four US missile strikes were reported in Pakistan's semi-autonomous tribal belt last year, down from 101 reported in 2010, according to AFP tallies.
The United States had until now refused to discuss drone strikes publicly, but the programme has dramatically increased as the Obama administration looks to withdraw all foreign combat troops from Afghanistan by the end of 2014.
In October, US Defence Secretary Leon Panetta acknowledged the CIA's drone programme, but did not specifically indicate they were used in Pakistan.
When asked by AFP if Obama's remarks signalled a change in US policy about the drone programme, a White House spokesperson refused to comment.
The Pakistani government is understood to agree to the programme despite popular opposition at home. Drones have reportedly killed dozens of al-Qaeda and Taliban operatives and hundreds of low-ranking fighters since 2004.
But the missile strikes fuel widespread anti-American resentment, which is running especially high in Pakistan since US air strikes inadvertently killed 24 Pakistani soldiers in November.
A US-Nato investigation blamed the deaths on a litany of errors and botched communications on both sides. But Pakistan rejected the findings, insisting the strikes had been deliberate.
Obama said drones had "not caused a huge number of civilian casualties" and that it was "important for everybody to understand that this thing is kept on a very tight leash".
Islamabad is now reviewing its entire alliance with the United States and has kept its Afghan border closed to Nato supply convoys for two months.
It ordered US personnel to leave Shamsi air base in western Pakistan, widely believed to have been a hub for the CIA drone programme, and is thought likely to only re-open the Afghan border by exacting taxes on convoys.
The State Department said on Monday it had used small, unarmed surveillance drones to protect US diplomats in so-called "critical threat environments" overseas.
The news emerged after the New York Times reported that Iraqi officials have expressed outrage at US use of a small fleet of drones to help protect the embassy, consulates and American personnel in Iraq.
"The State Department has always used a wide variety of security tools and techniques and procedures to ensure the safety of our personnel and our facilities," spokesperson Victoria Nuland said.
"We do have an unmanned aerial vehicle (UAV) programme used by the State Department," she said, adding the UAVs are "tiny" and "not capable of being armed" but designed to provide pictures of US government facilities.