"A US soldier was killed in action while conducting operations against ISIS-Khorasan in Afghanistan," US Navy Captain Bill Salvin said, referring to a provincial affiliate of the terrorist group.
"The soldier was mortally wounded late Saturday during an operation in (eastern) Nangarhar Province. More information will be released as appropriate," Salvin was quoted as saying by the official Twitter account of NATO's Resolute Support mission.
Nangarhar, which borders Pakistan, is a hotbed of ISIS terror and American forces have conducted a number of air strikes on jihadist bases in the area since August last year.
ISIS, notorious for their brutal reign of terror in Syria and Iraq, has been making inroads into Afghanistan in recent years. They are known to be comprised of disaffected Pakistani and Afghan Taliban, as well as Uzbek Islamists.
But the group has been steadily losing territory in the face of heavy pressure from both US air strikes and a ground offensive led by Afghan forces.
ISIS' strength has depleted to 600-700 fighters from 3,000 in early 2016, NATO has said, adding that it killed the top 12 ISIS commanders in Afghanistan last year.
The terrorists claimed a deadly assault on Afghanistan's largest military hospital last month, but survivors who spoke to AFP said the attackers chanted "Long live Taliban" in Pashto.