After weeks of expectation, with US military assets building up around the Middle East and rhetoric about possible strikes on Iran, Israel fired the first shot on Saturday morning, local time.
Israeli Defence Minister Israel Katz announced his nation had conducted a "pre-emptive strike", saying it was to "remove threats" to Israel.
US President Donald Trump then confirmed the American military had begun "major combat operations" and echoed Israel's reasoning, with the US defence ministry dubbing its strikes Operation Epic Fury.
Iran, which threatened a "crushing response", has since responded with its own missile strikes on Israel and several US bases in neighbouring Arab countries, including the UAE, Qatar, Bahrain, and Kuwait.
Where have the strikes hit, who were the targets, what was the response, and why now? Here's what we know.
Where have the strikes hit?
There were reports of the initial strikes hitting Iran's capital, Tehran, and other cities around the country.
The Iranian Fars News Agency has reported blasts in Boushehr, Tabriz, Dezfoul, Nahavand, Khark Island and Kangavar, while Tasnim news agency reports blasts have been heard in Isfahan, Ilam and Qom.
As the strikes mounted, at least two news agencies, Tasnim and IRNA, reported they were subjected to cyber attacks.
Internet disruptions have also been reported throughout Iran, with NetBlocks, an internet status watchdog, reporting that Iran is at a "near-total internet blackout" with national connectivity at 4 per cent.
It is unclear if the blackout is a result of the strikes or authorities in Tehran limiting internet access in the country.
A strike on a girls school in Iran's southern city of Minab, where the paramilitary Revolutionary Guard has a base, killed at least 100 people according to Iranian officials.
Following the strike, the Iranian ambassador to the United Nations accused the US and Israel of committing a "war crime", saying it targeted civilian infrastructure and killed more than 100 children at the school.
Who were the targets?
While Iran's nuclear facilities were expected to be targets, the first strike happened near the offices of Supreme Leader Ayatollah Ali Khamenei.
In later strikes, Israel said it was targeting military infrastructure in the country's west.
An Israeli official later said the ayatollah and Iranian President Masoud Pezeshkian were the targets of attacks, but the results were unclear.
An unnamed Israeli official told Reuters he had been killed and his body had been found.
It followed an address by Benjamin Netanyahu, who said there were "many signs that this dictator is gone".
Donald Trump said in a social media post that Iran's supreme leader had been killed, something later confirmed by Iranian state media.
The ayatollah's daughter, grandchild, daughter-in-law and son-in-law were also been killed in the US-Israeli strikes.
"Khamenei, one of the most evil people in history, is dead," Mr Trump wrote on Truth Social.
He told NBC News earlier in a phone interview that "most" of Iran's senior leadership was "gone", saying: "The people that make all the decisions, most of them are gone."
An Iranian source close to the establishment said several senior commanders of Iran's Revolutionary Guard and political officials had been killed. Reuters could not independently confirm the report.
The office of Iran's army chief, Major General Amir Hatami, said he was safe and "actively commanding the armed forces".
What was the response?
Within hours of the initial strike, Iran had fired several barrages towards Israel, most of them struck down by air defences.
Then Iran fired at US military bases, including the Al-Udeid Air Base in Qatar, Al-Salem Air Base in Kuwait, Al-Dhafra Air Base in the UAE, and the US base in Bahrain.
At least one woman was killed in Tel Aviv from an Iranian missile strike, according to Israel's rescue services responding at the scene.
Two people were killed by Iranian strikes targeting the Jurf al-Nasr area in Iraq's Babil province, according to the Iraqi army.
The UAE foreign ministry said one Pakistani national was killed in the strikes in Abu Dhabi.
Abu Dhabi Airport was also hit and confirmed an incident at Zayed International Airport that resulted in the death of an Asian national.
Most of these countries condemned the strikes and said they reserved the right to respond.
Most air travel in and out of all countries involved has been suspended, with governments warning their citizens to stay in place.
Why did this happen now?
Negotiations between the US and Iran over its nuclear program ended without a deal on Thursday, with Mr Trump expressing disappointment and warning "sometimes you have to use force".
Iran denies it is trying to develop nuclear weapons and had wanted any accord to include the lifting of US sanctions against it.
The US has been increasing diplomatic and military pressure on Iran in the weeks since an Iranian crackdown on protesters.
Last week, Mr Trump gave Iran a deadline of 10-to-15 days to make a deal. These attacks come before that deadline.
While rhetoric before the strikes centred on the idea Iran could produce nuclear weapons, in statements since both the US and Israel have played up the possibility of regime change in Iran.
Mr Trump called on Iranians to take control of their government when the US is finished.
"It will be yours to take. This will be probably your only chance for generations," he said.
Israel's Prime Minister Benjamin Netanyahu followed suit, saying their "joint action will create the conditions for the courageous Iranian people to take their destiny into their own hands".
Both leaders are also framing Iran as a common enemy, saying it is an "evil regime" that has called for "death to Israel" and "death to America" for 47 years.
ABC/Reuters
