Iran's state run radio reported: "The Americans have been defeated in Palestine since the butcher of the Palestinians, who intended to destroy the Palestinian Intifada, has come to his end," the radio quoted Khamenei as saying to a group of visitors.
On Thursday, Mahmoud Ahmadinejad, the Iranian president, said he hoped for the death of Sharon, the Israeli prime minister. Khamenei also sent a message to pilgrims in Islam's holiest city of Makka, Saudi Arabia.
Khamenei said: "The US Middle East policy faced major obstacles... The failure of the policy has turned it into a weapon against its designers.
"Today on the one hand there is Iraq, and on the other hand Palestine and Lebanon, displaying the weakness and powerlessness of the US and Zionism.
"I urge Muslim nations to support and protect Palestinians and Iraqis, as well as backing up peace and stability in Lebanon and Syria," the supreme leader added.
Iran and the US have regularly clashed over issues ranging from the War on Terror and the Middle East peace process to Iran's controversial nuclear programme.
Washington charges Tehran is trying to develop nuclear weapons, while Iran says its nuclear programme has the sole aim of making fuel for atomic reactors that would generate electricity.
Iran and the US have not had diplomatic relations since 1979 when students stormed the US embassy in Tehran and took American diplomats hostage for 444 days.
Ahmadinejad called the Holocaust a "myth" in December. After global outrage over the comments, he said that Europeans should cede some of their territory for a Jewish state.