Air raid sirens sounded across Israel on Friday as authorities urged the public to take shelter.
Missiles were seen over Tel Aviv's skyline, with the military saying Iran had fired two salvos.
Israel's military said Iran fired fewer than 100 missiles and most were intercepted or fell short.
The US military helped shoot down Iranian missiles headed for Israel, two US officials said.
Israel's Channel 12 said two people were critically injured, eight moderately and 34 slightly from shrapnel.
Several buildings were struck in the attack.
The Israeli strikes on Iran and the Iranian retaliation raised fears of a broader regional conflagration, although Iran's allies Hamas in Gaza and Hezbollah in Lebanon have been decimated by Israel.
Iranian state news agency IRNA said Tehran launched hundreds of ballistic missiles at Israel after Israel blasted Iran's huge Natanz underground nuclear site and killed its top military commanders.
Iran says its nuclear program is only for peaceful purposes, while Western countries have long accused Iran of refining uranium at Natanz to levels suitable for a bomb rather than civilian use.
The above-ground pilot enrichment plant at Natanz had been destroyed, UN nuclear watchdog chief Rafael Grossi told the Security Council on Friday.
He said the UN was still gathering information about Israeli attacks on two other facilities, the Fordow fuel enrichment plant and at Isfahan.
Iran's Supreme Leader Ayatollah Ali Khamenei accused Israel of starting a war, and a senior Iranian official warned that revenge would be painful.
Iran's UN envoy Amir Saeid Iravani said 78 people, including senior military officials, were killed in Israel's strikes on Iran and more than 320 people were wounded, most of them civilians.
He accused the US of being complicit in the attacks and said it shared full responsibility for the consequences.
Israel's operation "will continue for as many days as it takes to remove this threat", Israeli Prime Minister Benjamin Netanyahu said in a TV address.
"Generations from now, history will record our generation stood its ground, acted in time and secured our common future."
Netanyahu, who for decades has raised the alarm about Iran's nuclear program, said he authorised the assault to prevent Iran building nuclear weapons - an objective Tehran denies.
Israel's UN envoy Danny Danon said intelligence had confirmed that within days Iran would have produced enough fissile material for multiple bombs.
Iran has long insisted its nuclear program is for civilian purposes only.
The UN nuclear watchdog concluded this week that it was in violation of its obligations under the global non-proliferation treaty.
US President Donald Trump said it was not too late for Tehran to halt the Israeli bombing campaign by reaching a deal on its nuclear program.
Tehran had been in talks with the Trump administration on a deal to curb its nuclear program to replace one that Trump abandoned in 2018.
Tehran rejected the last US offer.
The price of crude leaped on fears of wider retaliatory attacks across the oil-producing region.
In a phone interview with Reuters, Trump said nuclear talks between Tehran and the United States, scheduled for Sunday, were still on the agenda though he was not sure if they would take place.
"We knew everything," Trump said of the Israeli attack plans.
"I tried to save Iran humiliation and death. I tried to save them very hard because I would have loved to have seen a deal worked out," Trump said.
Two regional sources said at least 20 Iranian military commanders were killed, a stunning decapitation reminiscent of Israeli attacks that swiftly wiped out the leadership of Lebanon's once-feared Hezbollah militia in 2024.
Iran also said six of its top nuclear scientists had been killed.
Among the generals killed were the armed forces chief of staff, Major General Mohammad Bagheri, and the Revolutionary Guards chief, Hossein Salami.
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