Israel's military said more than 100 drones, which Iraqi security sources said were seen flying over the country from Iran, would take hours to reach their targets. Israeli Channel 12 said some had been shot down over Syria or Jordan.
Iran's state news agency cited a source saying its military had also launched a first wave of ballistic missiles against Israel.
Iran has vowed retaliation for what it called an Israeli strike on its Damascus consulate on April 1 that killed seven Guards officers including two senior commanders and said its strike was a punishment for "Israeli crimes". Israel has neither confirmed nor denied responsibility for the consulate attack.
"Should the Israeli regime make another mistake, Iran's response will be considerably more severe," the Iranian mission to the United Nations said, warning the US to "stay away". However, it also said Iran now "deemed the matter concluded".
US President Joe Biden, who on Friday had warned Iran against an attack, cut short a visit to his home state of Delaware to meet national security advisers in the White House Situation Room, an official said. He pledged to stand with Israel.
The Gaza war between Israel and Hamas, now in its seventh month, has driven up tensions in the region, spreading to fronts with Lebanon and Syria and drawing long-range fire at Israeli targets from as far away as Yemen and Iraq.
British maritime security company Ambery said in a statement that drones were also reportedly launched against Israel by Yemen's Iran-aligned Houthi group.
Those clashes now threaten to morph into a direct open conflict pitting Iran and its regional allies against Israel and its main supporter the United States, with regional power Egypt urging "utmost restraint".
US and British warplanes were involved in shooting down some Israel-bound drones over the Iraq-Syria border area, Channel 12 reported. Three US officials said the US military had shot down drone aircraft without saying how many.
ESCALATION
"This is a severe and dangerous escalation. Our defensive and offensive capabilities are at the highest level of readiness ahead of this large-scale attack from Iran," said Israel's military spokesperson Rear Admiral Daniel Hagari.
Israeli Prime Minister Benjamin Netanyahu, whose official jet took off shortly after the attack began, convened the war cabinet at a military headquarters in Tel Aviv, his office said.
Israel's military said sirens would sound in any threatened areas and that its defences were poised to deal with the drones, which it said were "explosive".
"We are used to having around 20 seconds to get to shelters when missiles come in. Here, the warning comes hours ahead of time. It naturally raises the anxiety level among the Israeli public," said Nir Dvori, a Channel 12 TV correspondent on social media.
Israel's military told residents of the Israeli-occupied Golan Heights to stay close to bomb shelters, putting the area on standby for possible impact from drone strikes.
Israel and Lebanon said they were closing their airspace on Saturday night. Jordan, which lies between Iran and Israel, had readied air defences to intercept any drone or missile that violated its territory, two regional security sources said.
Residents in several Jordanian cities said they heard heavy aerial activity.
Syria, an ally of Iran, said it was putting its ground-to-air defence systems around the capital and major bases on high alert, army sources there said.
CONDEMNATION
The European Union, Britain, France, Mexico, Czechia, Denmark, Norway and the Netherlands all condemned Iran's attack.
Israel has been bracing for an Iranian response to the Damascus consulate strike since last week, when Iran's Supreme Leader Ayatollah Ali Khamenei said Israel "must be punished and shall be" for an operation he called equivalent to one on Iranian soil.
Biden said on Friday that his only message to Iran was "Don't", but added that "we are devoted to the defence of Israel."
Iran's main ally in the region, the Lebanese Shi'ite group Hezbollah that has been exchanging fire with Israel since the Gaza war began on October 7 last year, said early on Sunday it had fired rockets at an Israeli base.
Earlier on Saturday, Iran's state-run IRNA news agency reported that a Guards helicopter had boarded and taken into Iranian waters the Portuguese-flagged MSC Aries.
MSC, which operates the Aries, confirmed Iran had seized the ship and said it was working "with the relevant authorities" for its safe return and the wellbeing of its 25 crew.
MSC leases the Aries from Gortal Shipping, an affiliate of Zodiac Maritime, Zodiac said in a statement, adding that MSC is responsible for all the vessel's activities. Zodiac is partly owned by Israeli businessman Eyal Ofer.
Israeli Foreign Minister Israel Katz accused Iran of piracy.
