The only president Afghanistan has known since the 2001 US-led invasion said the United States wanted war in Afghanistan "because of its own interests."
Karzai's relationship with the US has grown increasingly fragile in recent years, but the US-Afghan relationship may get a reset yesterday, when President-elect Ashraf Ghani Ahmadzai will be sworn in.
The United States has spent more than USD 100 billion on aid in Afghanistan since 2001 to train and equip the country's security forces, to pave crumbling dirt roads, to upgrade hospitals and to build schools.
But Karzai in his speech thanked a slew of countries for their help India, Japan, China, Iran, Turkey, Saudi Arabia, South Korea and Germany without mentioning the US.
The speech fingered the US and the military leaders of neighbouring Pakistan as the powers backing perpetual war. "If America and Pakistan really want it, peace will come to Afghanistan," Karzai said.
"War in Afghanistan is based on the aims of foreigners. The war in Afghanistan is to the benefit of foreigners. But Afghans on both sides are the sacrificial lambs and victims of this war."
More than 2,200 US forces have died in Afghanistan operations since 2001. Nearly 20,000 have been wounded.
The United Nations says that some 8,000 Afghan civilians have been killed in the conflict over the last five years alone. In his final year in office Karzai refused to sign a security agreement with the US that would set the legal framework to allow about 10,000 American military advisers and trainers to stay in the country next year.
Ghani Ahmadzai has said he will sign it. Karzai's relationship with President Barack Obama is seen as weak, though Secretary of State John Kerry appears to have a rapport with the outgoing Afghan president.
Dozens of telephone calls made by Kerry to the two top presidential candidates helped bring about a political deal signed Sunday for a unity government.
Ghani Ahmadzai was announced by the election commission as winner of a June runoff election plagued by a huge amount of vote fraud. Opponent Abdullah Abdullah will fill the newly created role of government chief executive.