Mr Karzai, who is in Washington, told CNN air strikes were "not acceptable".
Afghan officials say more than 100 civilians died when US jets attacked targets in the western Farah province.
The incident overshadowed a summit on Wednesday between the President Barack Obama, Mr Karzai, and his Pakistani counterpart Asif Ali Zardari.
"We demand an end to these operations... an end to air strikes," Mr Karzai told CNN.
He said the deaths were "definitely" the result of US air strikes and not Taleban militants, as some US military officials had suggest - BBC News Story
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