It marked the first time in the war that Israel's nuclear research centre has been targeted.
The Israeli military said its defences were not able to intercept missiles that hit the southern cities of Dimona and Arad. Dozens of people were injured, emergency services said.
"The war is not close to ending," said Israel's army chief, General Eyal Zamir.
Iran's health ministry said more than 1500 people have been killed there so far, the state broadcaster reported.
Earlier, Iran targeted the joint UK-US Diego Garcia military base in the Indian Ocean about 4000km away, suggesting that Tehran has missiles that can go farther than previously acknowledged - or that it had used its space program for an improvised launch.
The Israel Defense Forces said the strike showed iran posed a global threat.
"The Iranian terrorist regime poses a global threat. Now, with missiles that can reach London, Paris or Berlin," it said on X.
Residents said Iran's capital saw heavy airstrikes as they marked the end of the holy month of Ramadan.
The US and Israel have offered shifting rationales for the war, from hoping to foment an uprising that topples Iran's leadership to eliminating its nuclear and missile programs and its support for armed proxies. There have been no signs of an uprising, while internet restrictions limit information from Iran.
The war's effects are felt far beyond the Middle East, raising food and fuel prices.
It is not clear how much damage Iran has sustained in the US and Israeli strikes that began February 28 - or even who is truly in charge. Supreme Leader Ayatollah Mojtaba Khamenei has not been seen in public since being named to the role.
Israel denies responsibility for attack on Natanz
There was no leakage after the strike on the Natanz nuclear facility, nearly 220km southeast of Tehran, the Iranian judiciary's official news agency, Mizan, said.
The UN nuclear watchdog has said the bulk of Iran's estimated 440kg of enriched uranium is elsewhere, beneath the rubble at its Isfahan facility. The International Atomic Energy Agency said on X it was looking into the strike.
Israel's military said it was "not aware" of a strike by it there.Â
The Pentagon declined to comment. Russian Foreign Ministry spokesperson Maria Zakharova said such strikes posed a "real risk of catastrophic disaster throughout the Middle East".
Iran later retaliated, targeting Israel's nuclear program. Israel is believed to be the only Middle East nation with nuclear weapons, though its leaders refuse to confirm or deny their existence.
The IAEA said on X it had not received reports of damage to the Israeli centre or abnormal radiation levels.
The Natanz facility was also hit in the first week of the war and in the 12-day war last June.
