"It was an incident early this afternoon in Paktika province between a US patrol and enemy forces," Major Mark McCann said on Monday.
"As a result, one US soldier was killed and two were wounded," he said, adding he had no further details on the incident.
The wounded soldiers were evacuated to a US medical facility in Khost province and were in stable condition, McCann said.
South-eastern Afghanistan, which borders Pakistan's tribal regions, has been the site of recent anti-US military attacks.
On 21 October, three US soldiers and their Afghan interpreter were wounded in the same province when a bomb exploded as their convoy passed.
On 16 October two US soldiers died in central Uruzgan province, one of the former strongholds of the Taliban. They too were killed by a roadside device.
The US-led force of 18,000 troops has been in the country
hunting al-Qaida and Taliban fighters since the US military toppled the Taliban regime three years ago. Some 16,000 of the troops are American.
More than 140 soldiers have died in Afghan operations since the start of US-led military operations.