President Joe Biden has promised Israel "ironclad" US support amid fears that Tehran could launch reprisals for an attack that killed senior Iranians.
Mr Biden warned that Iran is threatening to launch a "significant attack" after Israel struck the Iranian consulate in Syria ten days ago.
"We're going to do all we can to protect Israel's security," he added.
Earlier on Wednesday, Iran's leader said the Israeli attack in Damascus was equivalent to an attack on Iran itself.
"When they attacked our consulate area, it was like they attacked our territory," Ayatollah Ali Khamenei said in a televised speech.
Thirteen people were killed in the 1 April attack on the Iranian consulate building, including senior Iranian military leaders.
Israel has not claimed responsibility for the attack, but is widely considered to have been behind it.
US and Israeli forces in the region have been put on high alert in the days since.
Mr Biden's remarks came as he was speaking to journalists at the White House on Wednesday alongside Japanese Prime Minister Fumio Kishida.
"As I told Prime Minister Netanyahu, our commitment to Israel's security against these threats from Iran and its proxies is ironclad — let me say it again, ironclad," Mr Biden said.
His comments come one day after Mr Biden, in an interview, called for a ceasefire in Gaza and said he disagreed with Mr Netanyahu's war strategy.
"I think what he's doing is a mistake. I don't agree with his approach," he said in an interview with Univision that was recorded a week ago.
It also comes nearly a week after a tense phone call between Mr Biden and Mr Netanyahu in the wake of the Israeli killing of seven humanitarian aid workers in Gaza.
Mr Biden has sharpened his rhetoric over Israel's conduct in the nearly six-month-old war sparked by Hamas's 7 October attack, and voiced his growing frustration with Mr Netanyahu.
US officials have been attempting to send a message to the Iranians that, despite differences of opinion between Mr Biden and Mr Netanyahu, any attack on Israel will met with an aggressive US response.
In an effort to ease tensions, the foreign ministers of Saudi Arabia, the UAE, Qatar and Iraq spoke to their Iranian counterpart this week, according to Axios.
The ministers were asked to convey a message from Mr Biden's senior Middle East advisor, Brett McGurk, about the need to de-escalate.
According to Gaza's Hamas-run health ministry, more than 33,000 people - mostly women and children - have been killed in the Israeli incursion.
The conflict was sparked by Hamas's killing of more than 1,200 people in Israel and the taking of 240 hostages in its October attack.
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