Iran's proxies and allies also carried out coordinated attacks on Israeli positions as sirens sounded in many places and AFP correspondents heard blasts in the skies above Jerusalem early Sunday.
Iran had repeatedly threatened to retaliate against Israel for a deadly April 1 air strike on its Damascus consular annexe, and Washington had warned repeatedly in recent days that the reprisals were imminent.
"Iran launched UAVs from its territory towards the territory of the state of Israel," military spokesman Rear Admiral Daniel Hagari said in a televised statement.
"We are working in close cooperation with the United States and our partners in the region in order to act against the launches and intercept them."
People in Jerusalem sought cover, while some residents stockpiled water.
"As you can see it's empty, everybody is running home," said Eliyahu Barakat, a 49-year-old grocery shop owner in Jerusalem's Mamilla neighbourhood.
US President Joe Biden reiterated Washington's "ironclad" support for Israel after an urgent meeting with his top security officials on the spiralling crisis.
Iran's Revolutionary Guards confirmed a drone and missile attack was launched against Israel in retaliation for the Damascus strike which killed seven Guards, two of them generals.
The Guards said ballistic missiles were fired almost an hour after the slower moving drones.
Hundreds of Iranians gathered in Tehran's Palestine Square waving Iranian and Palestinian flags to celebrate the unprecedented military action against Israel.
The Israeli army said Iran had launched a "massive swarm of over 200 killer drones, ballistic missiles and cruise missiles".
"So far, we've intercepted the vast majority of incoming missiles," Hagari said.
The army said it had scrambled dozens of fighter jets to intercept "all aerial threats".
Iran's allies in the region joined the attack, with Yemen's Huthi rebels also launching drones at Israel, according to security agency Ambrey. Lebanon's Hezbollah movement announced it had fired rockets at Israeli positions in the annexed Golan Heights around the same time, as well as a second barrage hours later.
Tehran's official IRNA news agency said the attack -- which comes against the backdrop of the ongoing war between Israel and Palestinian militant group Hamas in the Gaza Strip -- had dealt "heavy blows" to an air base in the Negev desert, but the Israeli army said there had only been minor damage.
- 'Stay away' -
The Iranian mission to the United Nations warned Washington to keep out of Iran's conflict with Israel.
"It is a conflict between Iran and the rogue Israeli regime, from which the U.S. MUST STAY AWAY!" it said.
It added that it hoped its action to punish the strike on its diplomatic mission would lead to no further escalation and "the matter can be deemed concluded".
But despite Tehran's warning not to get involved, US forces took part in shooting down drones aimed at Israel.
Biden said in a later statement that the United States had "helped Israel take down nearly all of the incoming drones and missiles".
Early Sunday, the office of Israeli Prime Minister Benjamin Netanyahu said he had spoken with Biden.
British Prime Minister Rishi Sunak condemned Iran's "reckless" action and pledged his government would "continue to stand up for Israel's security".
The UK defence ministry said it had moved several additional fighter jets to the region which stood ready to "intercept any airborne attack within range".
France echoed the commitment to Israel's security. "In deciding to take this unprecedented action, Iran has reached a new level of destabilisation," Foreign Minister Stephane Sejourne said.
Egypt, which regularly acts as a mediator between Israel and the Palestinians, said it was in "direct contact with all sides to the conflict to try to contain the situation".
Saudi Arabia, meanwhile, expressed concern at the escalation and called on "all parties to exercise utmost restraint and spare the region and its peoples from the dangers of war".
The UN Security Council was to meet at around 2000 GMT Sunday to discuss the crisis at Israel's request, its current president Malta said.
Biden said he would also convene his fellow leaders of the G7 group of wealthy nations on Sunday to coordinate a "united diplomatic response" to Iran's "brazen" attack.
- Israel 'prepared' -
Shortly before the launches, 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.
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 Jordan, Iraq and Lebanon announced they were temporarily closing their airspace.
Israel said it was closing its own airspace from 2130 GMT.
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 as it headed 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.
Indian official sources said late Saturday there were 17 Indian citizens on board the Aries, while the Philippine government said Sunday that four of its nationals were also aboard.
Both Israel and the United States denounced the seizure as piracy, with Israel also demanding the Guards be declared a "terrorist organisation" by the European Union.
- Gaza truce stalemate -
The Gaza war began with the unprecedented October 7 attack by Hamas against Israel, resulting in the deaths of 1,170 people, mostly civilians, according to an AFP tally based on Israeli figures.
Israel's retaliatory offensive has killed at least 33,686 people in Gaza, mostly women and children, according to the territory's Hamas-run health ministry.
Israel's military said Saturday it had struck more than 30 Hamas targets across Gaza.
In the main central city of Deir al-Balah, fire burned in the rubble of a destroyed mosque.
Israel's military "demanded that the whole area be evacuated" before it was "wiped out in minutes", said Abdullah Baraka, a witness.
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 militant 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".
burs/kir/jkb/smw/mtp
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