He said that Europe and America were being manipulated by "murderous Zionists".
"Today, the Zionist regime is on a definite slope to collapse and there is no way for it to get out of the cesspool created by itself and its supporters," he said.
The comments were denounced as anti-Semitic by pro-Israeli groups in the US, while Israeli President Shimon Peres said the speech echoed a literary forgery published in the 1900s that posited a global Jewish and Masonic conspiracy to rule the world.
"This is the first time in the history of the UN that the head of a state is appearing openly and publicly with the ugly and dark accusations of the Protocols of the Elders of Zion," Mr Peres said.
Mr Ahmadinejad also accused the US and Nato of being "aggressors" in Iraq and Afghanistan, and of starting wars "in order to win votes in elections".
He added: "[The] American empire in the world is reaching the end of its road, and its next rulers must limit their interference to their own borders."
He said that six years after Saddam Hussein's regime had been ousted in Iraq, "the occupiers are still there".
"Millions have been killed or displaced, and the occupiers, without a sense of shame, are still seeking to solidify their position," he said.
On Monday, Iran was asked by the UN's nuclear watchdog, the IAEA, for a full response to concerns about its nuclear programme.
The agency's head, Mohamed El Baradei, said that without more information from Iran, the IAEA could not provide assurances.
But Mr Ahmadinejad told the assembly that "a few bullying powers" were seeking to stop Iran's peaceful nuclear activities by exerting pressure on Iran "and also through threatening and pressuring the IAEA".
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