"Targets are chosen with extreme care, factoring in concepts like necessity, proportionality, and an absolute obligation to minimise loss of innocent life and property damage," a US counterterrorism official said.
But the numbers show that more than 90 per cent of the 500 people killed by drones since mid-2008 are lower-level fighters, raising questions about how much the CIA knows about the targets, experts said.
Only 14 of those killed are considered by experts to have been high ranking members of al-Qaeda, the Taliban or other groups.
"Just because they are not big names it does not mean they do not kill. They do," the counterterrorism official said.
The US tally of combatant and non-combatant casualties is sharply lower than some Pakistani press accounts, which have estimated civilian deaths alone at more than 600.
Analysts have said that accurately estimating the number of civilian deaths was difficult, if not impossible.
"It is unclear how you define who is a militant and who is a militant leader," Daniel Byman, a counterterrorism expert at the Brookings Institution's Saban Center for Middle East Policy, said.
Jonathan Manes, a legal fellow at the American Civil Liberties Union, said: "It is impossible to assess the accuracy of government figures, unattributed to a named official, without information about what kind of information they are based on, how the government defines 'militants' and how it distinguishes them from civilians."
Former intelligence officials acknowledged that in many, if not most cases, the CIA had little information about those killed in the strikes.
Jeffrey Addicott, director of the Center for Terrorism Law at St Mary's University, said the CIA's goal in targeting was to "demoralise the rank and file".
"The message is: 'If you go to these camps, you're going to be killed,'" he added.
Critics say the expanded US strikes raise legal as well as security concerns amid signs that Faisal Shahzad, the suspect behind the attempted car bombing in New York's Times Square on Saturday, had ties to the Pakistani Taliban movement, known as Tehrik-e-Taliban Pakistan.
CIA-operated drones have frequently targeted the group over the past year in Pakistan, and its members have vowed to avenge strikes that have killed several of their leaders and commanders.
Shah Mehmood Qureshi, Pakistan's foreign minister, told CBS television channel that the US should not be surprised if anti-government fighters try to carry out more attacks.
"They're not going to sort of sit and welcome you [to] sort of eliminate them. They're going to fight back," Qureshi said.