Karzai's comments came after a week in which a relative of his was killed in a raid by foreign forces and he rejected an apology by the US commander of troops General David Petraeus for the deaths of nine children in a NATO strike.
"I would like to ask NATO and the US with honour and humbleness and not with arrogance to stop their operations in our land," Karzai said, visiting the dead children's relatives in Kunar province, eastern Afghanistan.
"We are very tolerant people but now our tolerance has run out."
He added that Kabul and his Western backers in the war against the Taliban were well aware that Pakistan's border areas, where insurgents have hideouts, ought to be the focus of international military campaigns.
Karzai also met relatives of those caught up in another incident in Kunar in which Afghan officials say 65 people died but NATO's International Security Assistance Force (ISAF) says left up to nine people injured.
The president cried as he held a girl who he said had her leg amputated following the latter attack.
A spokeswoman for ISAF could not immediately comment.
The latest Kunar incident, which happened as the children gathered firewood, forced the always-sensitive issue of civilian casualties caused by international troops back to the top of the political agenda in Afghanistan.
Karzai had already angrily rejected a public apology from Petraeus, the US commander of foreign troops, over the deaths.
US Defense Secretary Robert Gates also said he was sorry personally to Karzai during a visit to Afghanistan Monday.
Then on Thursday, it emerged that Karzai's father's cousin had been shot dead near his home in the family's village in Kandahar province, southern Afghanistan.
Karzai's spokesman Waheed Omer said the president was "extremely sad" at the news and "once again calls on NATO forces to avoid killing civilians."
A UN report Wednesday revealed that the deaths of Afghan civilians in the war had increased 15 percent to a record high last year, adding that insurgents were responsible for three-quarters of the killings.
The report recorded 2,777 civilian deaths last year, underscoring the level of violence in the country as foreign troops prepare to start handing control of security to Afghan forces in some areas from July.
Afghan security forces are due to take responsibility for security across the country by 2014, allowing international combat forces to withdraw.
There are currently around 140,000 international troops serving in Afghanistan, around two-thirds of them from the United States.
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