The soldier became the 89th member of the US armed forces to be killed in Afghanistan this year, the deadliest for US forces since they ousted the Taliban in late 2001.
The vehicle in which the two were travelling was hit on Tuesday by an improvised explosive device (IED) in the Tarin Kowt district of Uruzgan province, the US military said in a statement.
"They were part of a convoy to re-supply forces conducting operations aimed at defeating enemy forces in the area at the time of the detonation," the statement said.
The name and unit of the US soldier were withheld pending notification of relatives. The statement did not name suspects, but similar attacks have in the past been blamed on Taliban loyalists.
An investigation team had been flown to the site of the attack.
"We are saddened by our loss of our comrade and our thoughts are with his family," said US military spokesman Brigadier General Jack Sterling.
The US leads a force of nearly 20,000 troops, most of them American, to hunt down Taliban and other fighters in Afghanistan.
Also on Tuesday, a purported Taliban spokesman, Yousuf Ahmadi, said the group had killed an Indian worker they kidnapped at the weekend, but the authorities could not confirm the claim.
He said the Indian national had been shot dead after the Taliban received no response to a 48-hour deadline for the road construction company the hostage worked for to leave Afghanistan.
"Today at 6pm we killed the Indian roadworker with Kalashnikov shots, based on our earlier ultimatum," Ahmadi said in a telephone call from an undisclosed location.
"We had earlier given a 48-hour ultimatum. Nobody contacted us, that's why we killed the guy. We have thrown out his body."
The kidnapped man was snatched in southern Nimroz province on Saturday with an Afghan driver and two police guards. The driver was released on Monday. Ahmadi said the other two Afghans were "safe with us".
The Afghan government said it was trying to check Ahmadi's claim.