"The cause of the crash is under investigation; however, initial reporting indicates there was no enemy activity in the area at the time," a NATO statement said.
U.S. defense officials said the soldiers killed in the crash, which occurred in Afghanistan's southern Zabulprovince, were American. One person survived the crash but suffered injuries.
Zabul's deputy governor, Mohammad Jan Rasoulyar, said a crash had taken place in the Shah Joy district of Zabul.
A Taliban spokesman claimed on Twitter that Taliban militants had shot down a helicopter on Tuesday in the same district. The Taliban often claims responsibility for incidents in which it is not involved.
Aircraft crashes are not uncommon in mountainous Afghanistan.
The worst such incident was in August 2011 when the Taliban shot down a transport helicopter, killing all 38 people on board, including 25 U.S. special operations soldiers.
The Pentagon said that about 67,000 NATO-led troops remain in Afghanistan, including about 43,000 from the United States. Foreign forces are looking to curtail their decade-long fight there.
The United States continues to press Afghan President Hamid Karzai to sign a bilateral security deal that would allow Washington to keep some troops in Afghanistan beyond the end of next year.
(Reporting by Dylan Welch and Mirwais Harooni in Kabul, and David Alexander and Missy Ryan in Washington; Editing by Missy Ryan, Jonathan Oatis and John Wallace)