The airstrike came Friday in Kunar province, which borders Pakistan, the same area where a U.S. transport helicopter was downed on June 28 in the deadliest single blow to American forces since they ousted the Taliban in 2001.
"The president is extremely saddened and disturbed," said Jawed Ludin, President Hamid Karzai's chief of staff. "There is no way ... the killing of civilians can be justified. ... It's the terrorists we are fighting. It's not our people who should suffer."
A government team is on its way to the site to investigate the bombing, a Defense Ministry statement said.
Kunar provincial Gov. Asadullah Wafa told The Associated Press that an initial airstrike destroyed a house, and as villagers gathered to look at the damage, a U.S. warplane dropped a second bomb on the same target, killing 17 of them, including three women and children.
He said it was unclear who was killed in the initial attack in the tiny village of Chechal. "Maybe some militants were killed, but I don't know," he said. "The 17 people were killed in the second bombing."
The U.S. military said the attack was carried out "with precision-guided munitions that resulted in the deaths of an unknown number of enemy terrorists and noncombatants."