Iran's elite Revolutionary Guards launched extensive strikes against targets in Israel, Iranian media have reported, as Jordan, Iraq and occupied Palestinian territories watched for rockets or drones flying through its airspace.
Iran had repeatedly threatened to strike Israel in retaliation for a deadly April 1 air strike on its Damascus consular building and Washington had warned repeatedly in recent days that the reprisals were imminent.
A senior commander in the IRGC's Quds Force, Mohammad Reza Zahedi, was killed on April 1 in an airstrike on Iranian diplomatic premises in the Syrian capital, Damascus, that Iran blamed on Israel, prompting Iranian Supreme Leader Ayatollah Ali Khamenei to vow revenge.
Iran's dominant military force said in a statement that as part of its retaliatory response, it aims to target Israel through dozens of missiles and drones in Operation "True Promise" that also carries the password "O Messenger of God."
The Israeli military has also confirmed that Iran launched drones at Israel directly from its territory for the first time in the Islamic Republic's history.
The Guards said its ballistic missiles were fired almost an hour after the slower moving drones.
An Israeli army official said Iran had launched more than 200 attack drones and ballistic missiles at Israel.
Iran's allies in the region joined the attack with Yemen's Houthi rebels also launching drones at Israel, according to security agency Ambrey, and Lebanon's Hezbollah movement announcing rocket fire at Israeli positions in the annexed Golan Heights.
The official IRNA news agency said the attack had dealt "heavy blows" to an air base in the Negev desert, but the Israeli army said there had only been minor damage.
The White House said Washington would "stand with the people of Israel".
Iran has warned the United States to "stay away" from its conflict with Israel following the retaliatory drone and missile attack.
"Iran's military action was in response to the Zionist regime's aggression against our diplomatic premises in Damascus," Iran's Permanent United Nations mission said on X.
"Should the Israeli regime make another mistake, Iran's response will be considerably more severe," it said. "It is a conflict between Iran and the rogue Israeli regime, from which the US MUST STAY AWAY!"
The army statement came shortly after Prime Minister Benjamin Netanyahu said Israel was prepared for a "direct attack from Iran".
"Our defence systems are deployed, we are prepared for any scenario, both in defence and attack," the Israeli premier said in a televised statement, adding Israel had the backing of the United States and "many" other countries.
Iran's Revolutionary Guards had already seized an Israeli-linked container vessel in the Gulf earlier on Saturday, putting the whole region on alert.
Israel said it was closing schools nationwide while Lebanon and Iraq, which lie between Iran and Israel, announced they were temporarily closing their airspace.
Jordan's government spokesperson denied the kingdom announced a state of emergency and said media reports it did were baseless- adding that "there was no cause for concern among its citizens."
Israel said it would close its own airspace from 21:30 GMT.
Shortly after the ship seizure, the Israeli military warned Iran it would suffer the "consequences for choosing to escalate the situation any further".
The April 1 strike in Damascus, which killed 16 people, including two Iranian generals, had been widely blamed on Israel. Iran had repeatedly vowed to hit back, but had not specified how.
Iran's Revolutionary Guards seized a container ship "related" to Israel in the Strait of Hormuz on Saturday, which was now heading towards Iranian waters, Iranian state media reported.
The ship's operator, the Italian-Swiss group MSC, said it was working with the relevant authorities to ensure the wellbeing of the 25 crew onboard.
Both Israel and the United States denounced the seizure as piracy, with Israel also demanding that the Guards be declared a "terrorist organisation" by the European Union.
In Washington, National Security Council spokeswoman Adrienne Watson called on Iran "to release the vessel and its international crew immediately".
"Seizing a civilian vessel without provocation is a blatant violation of international law, and an act of piracy", she said.
President Joe Biden cut short a weekend trip to his home state of Delaware for urgent consultations in Washington, the White House said.
Israeli Foreign Minister Israel Katz postponed a planned visit to Hungary and Austria, his spokesman said.
An adviser to Iran's supreme leader said that Israel was in "complete panic" over Tehran's looming response.
"They don't know what Iran wants to do, so they and their supporters are terrified," senior adviser Yahya Rahim said.
Israel's offensive on Gaza has killed at least 33,686 people in Gaza, mostly women and children, according to the territory's health ministry.
Tensions have also flared in the Israeli-occupied West Bank, where a missing Israeli teenager was found dead on Saturday.
After the boy went missing near the city of Ramallah on Friday, hundreds of Jewish settlers backed by Israeli forces raided nearby Palestinian villages, torching cars and homes, leaving at least one villager dead and dozens injured.
Hamas said it had submitted its response to a Gaza truce plan presented by US, Qatari and Egyptian mediators at talks in Cairo this week.
The Palestinian group said it was sticking to its previous demands, insisting on "a permanent ceasefire" and the "withdrawal of the occupation army from the entire Gaza Strip".
Washington has ramped up pressure on Netanyahu to increase aid flows to Gaza where the United Nations warns of imminent famine.
Multiple press agencies have contributed to this report.