John Brennan faced repeated questions at his confirmation hearing over the targeted killings, which have even involved US citizens not charged with any crime.
Democratic senators demanded that the administration shared more information about the strikes with Congress and the public.
“It’s the idea of giving any president unfettered power to kill an American without checks and balances that’s so troubling,” said Oregon Democratic Senator Ron Wyden.
The hearing before the Senate intelligence committee had hardly begun before protesters opposed to the drone attacks disrupted the proceedings, heckling Mr Brennan before police cleared the hall.
As police removed protesters and other guests from the hearing room, one woman shouted: “This is a war criminal. He should not be confirmed.”
But Mr Brennan insisted: “We only take such actions as a last resort to save lives.”
The hearing shone a rare public spotlight on President Obama’s drone campaign and associated missile strikes involving hundreds of bombing raids by robot aircraft in Pakistan, Yemen and elsewhere.
The administration has sought to maintain strict secrecy over the raids but the threat of lawsuits and frustration from Congress has built pressure to defend the drone campaign publicly.