The US attorney general has acknowledged four US citizens have been killed in drone strikes since 2009.
In a letter to the Senate judiciary committee, Eric Holder defended the targeted killing of Anwar al-Awlaki.
But he said Awlaki's 16-year-old son as well as two other individuals were "not specifically targeted by the US".
The disclosure comes as President Barack Obama prepares to make a speech on counter-terrorism and the drone programme on Thursday.
The president will "discuss why the use of drone strikes is necessary, legal and just, while addressing the various issues raised by our use of targeted action", administration officials said.
His speech coincides with the signing of new "presidential policy guidance" on when drone strikes can be used, the White House said.
According to US news reports, the Pentagon has already started taking over responsibility from the CIA for drone strikes outside Pakistan.
The disclosure of the killings in Yemen and Pakistan marks the first formal public acknowledgement of the US citizen deaths in drone strikes.
"The president has directed me to disclose certain information that until now has been properly classified," Mr Holder wrote.
America's top law enforcement official defended the killing of Awlaki, whom he described as a "senior operational leader" of al-Qaeda in the Arabian Peninsula (AQAP).
Mr Holder said Awlaki was "intimately involved in detailed planning and putting in place plots against US persons".
Mr Holder added officials "appropriately concluded that [Awlaki] posed a continuing and imminent threat" to the US.
Awlaki, who was born in the US state of New Mexico, was killed in a missile strike from an unmanned plane in Yemen in September 2011. US officials announced his death but did not officially reveal he was killed by a drone.
Samir Khan, a naturalised US citizen who produced an online magazine promoting al-Qaeda's ideology, died in the same missile strike.
Awlaki's 16-year-old son Abdulrahman, who was born in Colorado, was killed in Yemen a month later.
Jude Kenan Mohammad, a North Carolina resident with a Pakistani father and an American-born mother, was arrested in Pakistan in 2008 after trying to enter a part of the country that is dominated by militants and is off-limits to foreigners.
He was charged with weapons possession and lacking the correct paperwork but disappeared after being granted bail.
According to his acquaintances, Mohammad is thought to have died in a strike in November 2011 in Pakistan's South Waziristan region, the New York Times reported.
Claims of transparency
Speculation of his death had been reported in local media in Raleigh, North Carolina, where he lived, but was not confirmed by US officials before Wednesday.
Mr Holder said the Obama administration had been transparent with Congress over its policy on drone strikes.
He cited an unclassified paper the justice department provided to congressmen that outlined the legal justification for the attacks.
In that document and in a speech at Northwestern University in March 2012, Mr Holder said strikes against US citizens could only be justified if the person posed an imminent threat of violent attack against the US, could not be captured, and the strike was conducted in a way that was consistent with the laws of war.
In his speech on national security, President Obama is also expected to address efforts to close the US detention camp at Guantanamo Bay, Cuba.
Last month, Mr Obama pledged a new push to transfer the remaining prisoners from the camp, saying it was "contrary to who we are" and harmful to US interests.