The strike was called in against Mullah Mustafa, who commanded about 100 men, in the western province of Ghor on Tuesday, the US military said in a statement.
The militant was targeted while he was travelling. "When he stopped in a remote area, he was joined by multiple militants," it said.
"Determining no civilians would be endangered, forces used precision aerial munitions to strike the group, killing Mustafa and as many as 16 other associated militants," it said.
The statement said the commander "had recently met with senior Taliban leaders, and reportedly had connections to Iranian Islamic Revolutionary Guard Corps — Quds Force."
He had been responsible for attacks along a highway linking the remote Ghor with the province of Herat, on the border with Iran, it said.
This could not be independently confirmed.
The Quds Force is the covert operations arm of Iran's Revolutionary Guards and is accused by American commanders of involvement in Iraq's bloody sectarian conflict.
Western officials have also said Tehran may be involved in the conflict in Afghanistan, where thousands of US troops are based, perhaps by supplying weapons to the Taliban or allowing them to transit through Iran.
Afghan President Hamid Karzai has however insisted that Iran is an important ally of his government and part of a regional solution, also including Pakistan, to the growing conflict overshadowing Afghanistan.
When the largely Sunni Taliban were in government between 1996 and 2001, Shiite Iran supported efforts to remove them.
The Al-Qaeda-linked Taliban were ousted in a US-led invasion that sent many of the militia's leaders into Pakistan where they were able to regroup to launch an insurgency that was its deadliest last year.
