WASHINGTON -- The U.S.-led International Security Assistance Force this week used aerial drones to kill 16 militants in volatile southern Afghanistan, a rare instance of the U.S. and its allies using a tactic more commonly employed against extremist targets across the border in Pakistan.

U.S. military officials said both attacks took place in Helmand province, one of the most violent regions of Afghanistan. In the first strike, ISAF said, a drone fired a Hellfire missile at a suspected militant safe house early Tuesday morning,...