"The first US shot on Iran would set the United States' vital interests in the world on fire," said Ali Shirazi, a mid-ranking cleric who is Khamenei's representative to the naval forces of the elite Revolutionary Guards.
"Tel Aviv and the US fleet in the Persian Gulf would be the targets that would be set on fire in Iran's crushing response," he said, according to the Fars news agency.
The United States and its top regional ally Israel have never ruled out attacking Iran over its nuclear drive, which the West fears could be aimed at making nuclear weapons.
There has been concern an attack against Iran could be imminent after it emerged Israel had carried out manoeuvres in Greece that were effectively practice runs for a potential strike against Iranian nuclear facilities.
Shirazi said "the Zionist regime is pressuring the White House leaders to plan a military assault on Iran" and Iran would react "if they commit such a stupidity."
It was not clear if he was referring to Tel Aviv as a city or as shorthand for the Jewish state as a whole, which the Islamic republic does not recognise.
His comments came as the Revolutionary Guards embarked on a new round of war games to sharpen their combat readiness amid continued tensions in the Iranian nuclear crisis.
The Great Prophet III manoeuvres by the missile and naval sections of the Revolutionary Guards are aimed at "improving the combat capability" of the forces, Fars reported.
The Guards are responsible for Iran's most significant ballistic missiles including the Shahab-3 missile, whose range puts Israel and US bases in the Gulf within reach.
However diplomatic efforts are also continuing. Iran has responded to an offer from world powers to end the nuclear crisis and diplomats are analysing what is said to be a complex answer from Tehran.
The offer from world powers proposes that Iran suspends uranium enrichment — the process which they fear could be used to make a nuclear weapon — in exchange for technological incentives.
But in the latest sign that Iran is not willing to compromise on the key question of enrichment, its envoy to London said world powers were "wasting their time" by insisting on this issue.
"The question of suspending uranium enrichment has become part of history and the West is just wasting its time by insisting on this illegal and illogical demand," Rassoul Movahedian told the official IRNA news agency.
There had been speculation that Iran was softening its hardline stance after several officials sounded optimistic notes about the package from world powers.
The comments calmed oil markets which had seen crude prices surge to record levels over fears that OPEC's number two producer was about to be the target of an attack.
Iran's response is a "complicated and difficult letter that must be thoroughly analysed," EU foreign policy chief Javier Solana, who presented the package, said on Monday.
He said he did not want to "give the impression of being too optimistic".
Meanwhile, the United States said that the different responses by Iranian officials showed there was debate within its system over how to answer the package.
It appears that "from… the varying public responses from various parts of the Iranian government that there is clearly a debate, or at least a discussion, going on within the Iranian government on how to respond," State Department spokesman Sean McCormack said.
Iran rejects the Western accusations and insists its nuclear programme is aimed solely at generating energy for a growing population whose fossil fuel reserves will eventually run out.
