Video images showed a US warplane falling out of the sky over Kuwait early on Monday.
Kuwaiti air defences mistakenly shot down three US F15 fighter jets flying in Iran-relatedoperations, the US military said on Monday. All six aircrew ejected safely and were in stable condition, it said.
After a weekend of bombing that killed Iran's supreme leader, dragged its neighbours into war and shut shipping traffic in the Gulf, markets opened on Monday with energy prices rising sharply, putting the global economic recovery at risk.
In the biggest US foreign policy gamble in decades, President Donald Trump launched the campaign alongside Israel against a foe that had tormented the United States and its allies for generations.
Trump repeated his calls on Iranians to rise up and overthrow their leaders, and said the air campaign could last weeks.
Within Iran, where residents have jammed highways to flee cities as bombs fell, there was uncertainty about the future and emotion ranging from apprehension to euphoria.
Many Iranians openly celebrated the death of Supreme Leader Ayatollah Ali Khamenei who ruled the country for 37 years and directed security forces that killed thousands of anti-government protesters at the start of this year.
But the conservative clerical leaders have shown no sign of yielding power.
Military experts say US and Israeli air power, with no armed force on the ground, may not be enough to drive them out.
Scores of Iranians have been reported killed in strikes, including several that hit apparent civilian targets.
"They are killing children, they are attacking hospitals. Is this the kind of democracy Trump wants to bring us? Innocent people were first killed by the regime and now by Israel and the United States," Morteza Sedighi, a 52-year-old teacher, said by phone from Tabriz.
A major new front in the war opened on Monday when Hezbollah, one of Tehran's principal allies in the Middle East, launched missiles and drones toward Israel in retaliation for the killing of Khamenei.
Israel responded with sweeping air strikes, which it said targeted the Hezbollah-controlled southern suburbs of Beirut and struck senior militants. Lebanese state news agency NNA said an initial tally showed 31 people had been killed and 149 injured.
Israel declared Hezbollah leader Naim Qassem a "target for elimination".
Inside Iran, explosions were heard across Tehran, while in Israel air raid sirens were triggered in Tel Aviv and Jerusalem.
Washington's allies in the Gulf have come under attack from Iranian missiles and drones.
Black smoke rose above the area around the US embassy in Kuwait, where there was a heavy presence of security, ambulances and fire trucks. There were loud blasts in Dubai and Samha in the UAE, and in Doha, capital of Qatar.
In the first strike to reach US allies in Europe, a drone hit Britain's Akrotiri air base in Cyprus overnight. Britain and Cyprus said the damage was limited and there were no casualties.
European allies have so far distanced themselves from Trump's decision to go to war, which Britain, France and others say fell short of the legal threshold of combating an imminent threat.
The Israeli military said its air force had established aerial superiority over Tehran, and a wave of strikes across the capital had targeted intelligence, security, and military command centres.
In interviews on Sunday, Trump said the campaign could last four weeks. A senior White House official said Washington would at some point talk with Tehran's leaders.
"President Trump said new potential leadership in Iran has indicated they want to talk and eventually he will talk. For now, Operation Epic Fury continues unabated," the official said.
It remained unclear what the longer-term prospects were for Iran to rebuild its leadership and replace Khamenei, 86.
Iran's elected president, Masoud Pezeshkian, said a leadership council composed of himself, the judiciary head and a member of the powerful Guardian Council had temporarily assumed the duties of supreme leader.
In an X post on Monday, Ali Larijani, a powerful adviser to Khamenei, said Iran would not negotiate with Trump. He said the US president had "delusional ambitions".
The first US casualties of the campaign, including the deaths of three service personnel on a base in Kuwait, were confirmed on Sunday. Trump paid tribute to them as "true American patriots".
An extended military campaign could pose a major political risk for Trump's Republican Party ahead of US midterm elections. Only around one in four Americans approve of the operation, according to a Reuters/Ipsos poll.
Meanwhile, the interruption to oil shipments through the Strait of Hormuz - where around a fifth of the world's oil trade passes along the Iranian coast - was a sudden jolt to global economies.
Oil prices leapt by double-digit percentages when trade opened on Monday.
Global air travel was also heavily disrupted as air strikes kept major Middle Eastern airports closed, including Dubai, the world's busiest international hub.