Two other Americans and six Afghan government troops were also injured in the battle in Paktika province, a military statement said.
The names of the dead soldiers were being withheld until relatives could be informed, the statement said. It gave no further details of the incident.
According to the U.S. Defense Department, 137 U.S. military personnel have now died during Operation Enduring Freedom, launched after the Sept. 11, 2001, attacks in the United States.
Some 99 of the fatalities have been in or around Afghanistan, and 54 of them have been troops killed in action.
More than 900 people have died in political violence across Afghanistan so far this year, and officials are braced for more bloodshed in the run-up to the landmark presidential elections on Oct. 9.
"Relatively high-ranking" members of both the Taliban and al Qaeda, as well as rebel Afghan faction Hezb-e Islami Gulbuddin, have held several meetings on how to derail the Oct. 9 vote, spokesman Maj. Scott Nelson said.
Citing intelligence reports, Nelson said the meetings were marked by growing alarm at intensifying efforts on both sides of the Afghan-Pakistani border to root out their activities.
"There have been several meetings between Taliban, al Qaeda and HIG members in Pakistan where they've raised serious concerns" about efforts to track them down as well as how best to attack the election, Nelson said told reporters.
Nelson said the participants in the meetings were "relatively high-ranking." He wouldn't elaborate or specify where they took place.
But the Pakistani government said the idea that such meetings could have taken place on its territory was "baseless."
"Al Qaeda and remnants of the Taliban regime are on the run in Pakistan. They cannot hold conferences," Foreign Ministry spokesman Masood Khan told reporters in Islamabad.
He said that the U.S. military was "looking in the wrong direction. The real danger lies inside Afghanistan" from warlords, drug traffickers and insurgents, he said.
Nelson said it was "certainly" possible that Osama bin Laden and other leaders of al Qaeda were in the rugged border region — on either side of the porous border.
Maj. Gen. Eric Olson, the operational commander of the U.S.-led force in Afghanistan, said this month that he had no fix on where bin Laden or his deputy, Ayman al-Zawahri, were located.
But he said he believed the al Qaeda leaders were still pulling some of the strings in the stubborn Afghan insurgency.
Olson cited a car bombing which killed about 10 people, including three Americans, at the office of a U.S. security company in the Afghan capital last month. He said a splinter group of al Qaeda with Pakistani and Afghan members may have been responsible.
Election workers have also been directly targeted, with 10 killed so far in a string of bombings and shootings, but the violence has failed to prevent millions of Afghans from registering to vote.
Nelson said the militants were divided over how best to thwart the election, which U.S.-backed interim President Hamid Karzai is widely expected to win.
"They talk, but I don't know how cohesive their strategies are," he said.
Karzai escaped a rocket attack on the U.S. helicopter carrying him to a provincial capital in eastern Afghanistan on Thursday in the second apparent attempt to assassinate the U.S.-backed interim leader since he took office in 2001.
Nelson said militants were also debating how to counter muscular operations by both the Pakistani military and Afghan and U.S. forces.
Thousands of Pakistani forces have carried out a string of bloody offensives in the Waziristan tribal region next to the border, bombing a suspected training camp and killing scores of suspected militants.
Nelson praised the Pakistani military for "very aggressive operations in the areas where we think these senior leaders are hiding. They've had quite a bit of success."
He said U.S.-allied forces had intensified their campaign against militants in the neighboring Paktika, Paktia and Khost provinces of Afghanistan.
The presidential election was originally set for June, but was postponed to September to allow more time to register voters and demobilize unruly militias. It was then moved to October, with parliamentary elections put off until next spring.
The persistent violence in Afghanistan threatens not only the elections but also another element of the country's reconstruction: aid workers. Doctors Without Borders, which has operated in the country for 24 years, pulled out this summer after five workers were killed.