Abu Waheeb, formerly a member of al-Qaeda in Iraq, was killed in a raid on Friday, according to the Pentagon.
“It is dangerous to be an Isil leader in Iraq and Syria nowadays,” spokesman Peter Cook said, using an alternative name for the group.
Waheeb has falsely been declared dead on several previous occasions.
He was killed travelling in a vehicle in a town near Rutba, in Anbar province, Mr Cook said.
The Pentagon said three other militants were killed in the raid, describing Waheeb as the IS “military emir for Anbar province”.
Born in 1986 and a former computer science student, Waheeb was often described on monitoring sites as a rising star among IS.
He was arrested by US forces in Iraq and sentenced to death but escaped prison in 2012, the following year gaining notoriety for killing a group of Syrian truck drivers travelling through Iraq.