Khamenei's reported killing came amid a major military combat campaign dubbed "Operation Epic Fury," following months of heated rhetoric and repeated warnings from Trump about military intervention in Iran.
The supreme leader's death heralds a seismic shift for a nation that has been controlled by a theocratic regime since the Islamic Revolution of 1979. It also creates a leadership vacuum in Tehran as heads of state worldwide grapple with the prospect of wider regional instability.
In a video message posted online, Trump urged Iranian civilians to seize control of their government after the strikes concluded. "When we are finished, take over your government," he said. "It will be yours to take."
U.S. and partner Israeli forces struck multiple targets, including Islamic Revolutionary Guard Corps command and control facilities, Iranian air defense capabilities, missile and drone launch sites and military airfields, U.S. Command announced in a statement.
There were no reports of American casualties and the damage to U.S. facilities was minimal. More than 200 people were killed and some 747 people have been injured in the attacks on Iran, a spokesperson for the Red Crescent Society said in an interview with the Iranian Students' News Agency.
"Twenty-four provinces across the country have been struck," Mojtaba Khaledi, the Red Crescent Society spokesperson, said.
Tehran retaliated with a barrage of missiles at Israel and at U.S. bases in several countries across the region, while officials, aid groups and world leaders warned the confrontation could spill beyond its initial targets, drawing in more countries and destabilize a region already on the edge.
Iran's Supreme National Security Council vowed in a statement that its armed forces would deliver a "crushing response" to the U.S. and Israeli attacks, as multiple U.S. allies in the region intercepted missiles targeting U.S. bases on their territory and throughout Israel.
Iran is attacking military facilities and not "Americans in their land," Iranian Foreign Minister Abbas Araghchi said in an interview with NBC News, adding that Tehran was interested in de-escalation and ready to talk once the joint U.S.-Israeli strikes end.
Trump, in his Truth Social post, said the U.S. "sought repeatedly to make a deal. We tried."
The United Nations Security Council held an emergency meeting Saturday, with Secretary-General António Guterres warning the attacks on Iran "carries the risk of igniting a chain of events that no one can control in the most volatile region of the world."