Republican Lindsey Graham is the first US government official to offer an estimate on the total number of fatalities in America's secretive drone war.
"We've killed 4,700," he was quoted as saying by the Easley Patch, a local website covering the small town of Easley in South Carolina.
"Sometimes you hit innocent people, and I hate that, but we're at war, and we've taken out some very senior members of Al Qaeda," Mr Graham told the Easley Rotary Club.
"It's a weapon that needs to be used," he said. "It's a tactical weapon. A drone is an unmanned aerial vehicle that is now armed."
Mr Graham's office did not dispute his reported remarks but suggested that he had not divulged any official, classified government figure.
A spokesman told AFP that the senator "quoted the figure that has been publicly reported and disseminated on cable news".
His remark was unprecedented, as US officials have sometimes hinted at estimates of civilian casualties but never referred to a total body count.
The strikes have been condemned by rights groups as extrajudicial assassinations.
"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 Mr Graham could have broken secrecy laws.
Several organisations have tried to calculate how many militants and civilians may have been killed in drone strikes since 2004 but have arrived at a wide range of numbers.
The figure cited by Mr 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.
US intelligence agencies and the White House have refused to divulge details about the strikes, which are officially termed classified, but officials have suggested that few if any civilians have been killed inadvertently.
In hearings this month on the nominee to lead the CIA, John Brennan, Senator Dianne Feinstein said she understood 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 runs 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.