"We've killed 4,700," said on Wednesday Republican Senator Lindsey Graham, a staunch supporter of the drone raids, openly cited a number that exceeds some independent estimates of the death toll.
"Sometimes you hit innocent people, and I hate that, but we're at war," Graham added.
It was the first time an American lawmaker or any government representative had referred to a total number of fatalities in the US drone strikes, which have been condemned by rights groups as extrajudicial assassinations.
The toll from hundreds of drone-launched missile strikes in the countries such as Pakistan, Yemen, Somalia and Afghanistan has remained a mystery, as US officials refuse to publicly discuss any details of the covert campaign.
Graham’s remark was unprecedented, as US officials have sometimes hinted at estimates of civilian casualties but never referred to a total body count.
"Now this is the first time a US official has put a total number on it," said Micah Zenko, a fellow at the Council on Foreign Relations.
If there was an official death toll estimate, it would be classified as secret, he added, raising the prospect that Graham could have broken secrecy laws.
The figure cited by Graham matches the high end of a tally by the London-based Bureau of Investigative Journalism. It says the number killed in drone strikes in Pakistan, Yemen and Somalia is between 3,072 and 4,756.
The Washington-based New America Foundation says there have been 350 US drone strikes since 2004, most of them during Barack Obama's presidency. And the foundation estimates the death toll at between 1,963 and 3,293, with 261 to 305 civilians killed.
In hearings this month on the nominee to lead the CIA, John Brennan, Senator Dianne Feinstein said she understood that the number of civilians killed was in the "single digits."
Drone strikes in Pakistan, Yemen and elsewhere are covert attacks overseen by the CIA, while bombing run by drones in Afghanistan fall under the US military's authority and are not cloaked in secrecy.
The Obama administration has insisted the "targeted killings" are "a last resort" against those plotting to attack the United States but who cannot be captured.
Opponents, however, say drone strikes amount to extrajudicial assassinations that sow resentment among local populations and lack oversight by Congress or courts.
Obama acknowledged for the first time this month that Americans needed more than just his word to be assured he was not misusing his powers in waging a secret drone war overseas.