Top Iranian hardline cleric Ayatollah Ahmad Janati accused the United States, Britain and Israel of "warring against God" and said their nationals should be made to feel unsafe wherever they are.
"If the Muslims do not know security, the Americans, British and the Israelis should not know security, for they are "moharebs" (warring against God)," Janati said at Friday prayers in Tehran, broadcast by state media.
"It is the duty of all Muslims and ardent non-Muslims to stand against the Americans, the British and the Israelis and to endanger their interests worldwide."
His comments sparked chants of "Death to the United States", "Death to England" and "Death to Israel" from the thousands who gathered for Friday prayers at Tehran University campus.
Janati, who heads the Guardians Council, a conservative vetting body, also distanced himself from the insurgency against the US-led occupation forces in Iraq by radical Shiite Muslim cleric Moqtada Sadr.
He urged Iraqis to unite behind Ayatollah Ali Sistani, the top Shiite cleric in Najaf, a holy Shiite city where Sadr's men are battling US troops.
The Americans "are here to fight Iraqi people, Kurds, Arabs, Shiites and Sunnis, in addition to Islam, so do not fight one another, and come under the umbrella of Ayatollah Sistani, for the clerics are your path to salvation," he said.
Iran has repeatedly called for an end to the occupation of neighbouring Iraq, a withdrawal of the US-led forces, and a transfer of power to Iraqis.
It has expressed anger at fighting in the Najaf and Karbala between coalition troops and Sadr's Mehdi Army militia, saying the violence "desecrated" sacred sites.