Ayatollah Ali Khamenei said on Sunday: "If you make a wrong move regarding Iran, definitely the energy flow in this region will be seriously endangered."
He also rejected demands that his country suspend nuclear work, which the US views as a cover for making weapons, and said the Islamic republic would not buckle in the face of "threats and bribes".
Iranian officials have in the past ruled out using oil as a weapon in the nuclear standoff with the West, but Khamenei pointed out that any action against his country could well disrupt supplies.
"You [the US] are not capable of securing energy flows in this region," he said in a speech to mark the anniversary of the death of the Ayatollah Ruhollah Khomeini, the founder of the Islamic republic.
Condoleezza Rice, the US secretary of state, reacted to Khamenei's comments by suggesting a wait-and-see approach.
"I think we shouldn't place too much emphasis on a move of this kind; after all Iran is very dependent on oil revenue," she said on Fox News Sunday.
|Iranians shouted anti-US slogans|
Asked whether Iranian leaders had already rejected the six-nation initiative by insisting there be no pre-conditions for new talks on their nuclear programme, Rice said Iran had not yet received the proposal and would need time to assess it.
"It's sort of a major crossroads for Iran, and it's perhaps not surprising that they will need a little bit of time to look at it," she said.
Speaking at Khomeini's mausoleum on the southern outskirts of Tehran, Khamenei said that "Iran is no threat to anyone".
"We have friendly relations with all the region and Asia," he said. "We have good and healthy relations with Europe, and in the close future, because they need our gas, these relations will become even better.
Khamenei said: "They accuse us of developing nuclear bombs. This is an absurd lie. We do not need nuclear weapons and bombs. We don't have any target to use them on. Using nuclear weapons is against Islamic rules.
"We will not impose the costs of building and maintenance of nuclear weapons on our people. Our explosive source is the power of our faith."
He also said that the United States had been weakened - and his speech was frequently interrupted by chants of "Death to America", "Death to Israel" and "We are ready!" from the thousands at the ceremony.
Khamenei said: "In Iraq you failed.
"You say you have spent $300 billion to bring a government in office that obeys you. But it did not happen. In Palestine, you made all attempts to prevent Hamas from coming to power and again you failed. Why do you not admit that you are weak and your razor is blunt."
"Why do you not admit that you are weak and your razor is blunt?"
Ayatollah Ali Khamenei
Khamenei did not explicitly refer to its nuclear programme in his speech, but he said: "We are committed to our national interests and whoever threatens it will experience the sharpness of this nation's anger."
He also praised the efforts of the country's nuclear scientists in developing home-grown nuclear technology.
Javier Solana, the EU foreign policy chief, is expected to hand over to Tehran incentives agreed by six world powers to persuade it to abandon plans to make nuclear fuel.
Iran has said enriching uranium for fuel is a national right.