Tehran, Iran - Ayatollah Ali Khamenei, Iran's supreme leader since 1989, was killed in the opening salvo of a massive US and Israeli attack, sparking a new wave of retaliatory missile strikes from Tehran on Sunday.

Iranian state television confirmed Khamenei's death early Sunday, hours after President Donald Trump announced the killing of the 86-year-old cleric he described as "one of the most evil people in History".

Huge crowds began gathering in Tehran and other cities to mourn the 86-year-old and demand revenge for his killing.

Iran's Revolutionary Guards vowed to launch the "most ferocious" operation in history against Israel and US bases, which are located in Gulf countries that were already counting the cost of an unprecedented series of deadly Iranian strikes.

Fresh explosions were heard in Doha, Dubai and Manama on Sunday, according to AFP journalists, as warning sirens sounded in central Israel with the military saying it was responding to Iranian missile fire.

Iran's state broadcaster said 27 US bases in the region, as well as Israel's military headquarters and a defense industries complex in Tel Aviv, were among the targets in a new wave of strikes.

Trump threatened that any retaliation from Tehran will lead to Iran being hit with a force that has "never been seen before".

He had earlier vowed no let-up in the strikes until the fall of the Islamic republic and urged security forces to stand down.

"This is the single greatest chance for the Iranian people to take back their Country," Trump said in a statement.

Israeli Prime Minister Benjamin Netanyahu also told Iranians that "this is your time to join forces, to overthrow the regime and to secure your future."

Iran's judiciary confirmed that Ali Shamkhani, a top advisor to Khamenei, and the head of Iran's powerful Revolutionary Guards, General Mohammad Pakpour, were both killed.

One prominent survivor, Ali Larijani, head of Iran's Supreme National Security Council, vowed defiance.

"The brave soldiers and the great nation of Iran will teach an unforgettable lesson to the international oppressors," he said.

Iran's parliament speaker also said that Tehran was prepared and had "considered all scenarios".

Trump and Netanyahu have "crossed our red lines" and "will suffer the consequences," said Mohammad Bagher Ghalibaf in a video carried on state TV.

Iranian President Masoud Pezeshkian and two top other officials would lead Iran in the transitional period following Khamenei's death, state television reported on Sunday.