The American was killed when Afghan and U.S. forces came under attack during a patrol Monday in southern Zabul province's Day Chopan district, triggering a firefight, the U.S. military said in a statement.
U.S. and coalition aircraft provided air support during the clash, it said.
Initial estimates showed that at least 16 suspected insurgents were killed, according to the statement.
"We are greatly saddened by the loss," a U.S. military officer, Brig. Gen. James G. Champion, was quoted as saying. "Afghan and U.S. forces will continue this search and attack mission to ensure there are no enemy safe havens in this region."
The deceased U.S. service member's name was being withheld pending notification of next of kin, the statement said.
Meanwhile, two American troops were wounded Tuesday when a roadside bomb exploded near their vehicle in eastern Ghazni province.
A U.S. military statement said both were in stable condition and were being evacuated to the main U.S. base in Afghanistan, Bagram Airfield, for medical treatment.
More than 17,000 U.S. forces are in Afghanistan, hunting Taliban and al Qaeda militants still active in the south and east of the country. Violence since March, following a winter lull in the rebellion, has claimed more than 900 lives.
The American casualty follows the deaths of three U.S. service members in eastern Afghanistan last Thursday. Two drowned when their Humvee vehicle slid into swollen river during a military operation east of the city of Jalalabad; a third was killed by a roadside bomb that exploded near a U.S. military vehicle in the eastern province of Paktika, near the Pakistan border.
More than 170 U.S. service members have died in and around Afghanistan since Operation Enduring Freedom was launched in late 2001 to oust the Taliban following the Sept. 11 attacks on America.
By Daniel Lovering