Speaking before the UN General Assembly in New York, Netanyahu said that "the most urgent challenge facing this body today is to prevent the tyrant of Tehran from acquiring nuclear weapons."
The Iranian regime, he said, "Is motivated by fanaticism… They want to see us go back to medieval times. Perhaps some of you think that this man and his odious regime, perhaps they threaten only the Jews. Well, if you think that, you're wrong. You're dead wrong," he said.
"The struggle against Iran pits civilization against barbarism," Netanyahu told the UN. "This Iranian regime is fueled by extreme fundamentalism."
Netanyahu also addressed Iranian President Mahmoud Ahmadinejad's denial of the Holocaust. During the speech, he waved the minutes of the Wansee Conference, in which Nazi officials planned the Final Solution. "Is this a lie? he said.
The PM also held up the architectural blueprints of the Auschwitz-Birkenau death camps that bear the signature of Hitler's deputy, Heinrich Himmler, which he received during a recent trip to Germany.
He praised those diplomats who boycotted Ahmadinejad's speech, but condemned those who allowed it: "To those who gave this Holocaust denier a hearing, I say on behalf of my people. ... Have you no shame? Have you no decency?... What a disgrace. What a mockery of the charter of the United Nations."
During the speech, Netanyahu criticized the world body for failing to pass any resolution denouncing Hamas rocket fire on Israel over the past eight years, and blasted the UN Human Rights Council for its "twisted standards."
The Council recently issued a report accusing Israel of war crimes in its war last winter against Palestinian terrorists in Gaza.
He said the report turns the victims into the aggressors and encourages terrorism.
Turning his attention to the fumbling Israeli-Palestinian peace process, Netanyahu said that Israel "wants peace and I believe that with goodwill and with hard work such a peace can be achieved.
"But it requires from all of us to roll back the forces of terror led by Iran that seek to destroy peace, that seek to eliminate Israel and to overthrow the world order."
President Shimon Peres phoned Netanyahu to congratulate him on his speech, as did most of cabinet members.
"The PM's speech restored the Jewish nation's honor before the UN and the entire world," one minister said.
Members of Israel's delegation to the General Assembly session, including Defense Minister Ehud Barak and Foreign Minister Avigdor Lieberman also congratulated Netanyahu.
Roni Sofer, Associated Press and Reuters contributed to this report