"Our position on drone strikes is clear and based on principles. Drone attacks are unlawful, counter-productive and hence unacceptable," Foreign Office spokesman Abdul Basit said in a text message sent to PTI.
"We cannot condone the violation of our sovereignty," he said.
Obama confirmed for the first time that US drones had targeted militants in Pakistan's tribal areas during a chat with users of Google+ and YouTube.
He said that a lot of these strikes have been in 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... 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," he said.
The drone campaign by the CIA has become an irritant in Pakistan-US ties largely due to growing anti-Americanism in Pakistan.
Rights groups have alleged that scores of civilians have died in the missile attacks.
US diplomatic cables leaked by WikiLeaks in 2010 showed that Pakistan's civilian and military leaders privately supported the US drone attacks despite public condemnation.
The CIA has scaled down drone attacks following a cross-border NATO air strike that killed 24 Pakistani soldiers in November.
Pakistan reacted to the NATO attack by closing all routes used to transport supplies to foreign troops in Afghanistan and forcing the US to vacate Shamsi airbase, which was a hub for CIA-operated drones.
Prime Minister Yousaf Raza Gilani ordered a comprehensive review of relations with the US and directed a parliamentary panel to frame new terms of engagement that will be debated by Parliament.