"I strongly oppose the use of Mother of All Bombs (MOABs) on Nangarhar and consider it as an obscene act and violence against our people, territory, environment and national sovereignty," Karzai said on Sunday.
Blasting the US for using the MOABs to kill a limited number of terrorists, he said that hazards of the bomb for Afghanistan and its environment are like atomic bombs.
Karzai also lashed out at the Afghan government for supporting the US attack, and said, "The use of this bomb is not acceptable at all and by carrying out such dreadful and violent operations against the Afghan people the US has no more right to make any claim in Afghanistan. Washington proved that it uses Afghanistan as a test field for its dangerous and lethal weapons."
Stressing that the Afghan people don’t allow foreigners to make any aggression against them, he said, "Therefore, by its Thursday operations, the US has lost the legitimacy for any claims and it should leave Afghanistan."
Friday saw global audiences awaking to news the US military had dropped a GBU-43/B MOAB against what it called the ISIS position in Afghanistan's Nangarhar province.
The Thursday event marked the use of the weapon on the battlefield for the first time in history.
The bomb is nicknamed the Mother of All Bombs for its 11-tonne blast yield and it is worth $16 million.
In relevant remarks after the bombing, Karzai called on his countrymen to "stop the USA" after what he said was Washington using Nangarhar province as a testing ground for the biggest non-nuclear weapon in the US arsenal.
"I vehemently and in strongest words condemn the dropping of the latest weapon, the largest non-nuclear bomb, on Afghanistan by US military," tweeted Karzai. "This is not the war on terror but the inhuman and most brutal misuse of our country as testing ground for new and dangerous weapons."
"It is upon us, Afghans, to stop the USA," he added.