Boris Johnson has accused US President Barack Obama of "hypocrisy" over his support for the UK remaining in the EU.
The London mayor, who backs EU exit, told the BBC the Americans "wouldn't dream of sharing [their] sovereignty" as the UK had done.
The US president is expected to repeat his support for Britain's EU membership when he visits the UK next week.
Backers of Remain dismissed Mr Johnson's remarks as "nonsense", citing US membership of Nato and trade bodies.
The White House has indicated Mr Obama is ready to offer his view on the issue but will stress the decision is for UK voters.
Speaking in Washington, Chancellor George Osborne said it was the "overwhelming view" of foreign governments and international institutions such as the IMF and Nato that the UK should remain.
Backing from Mr Obama could boost Prime Minister David Cameron's efforts to persuade the country to vote to remain in the EU in the 23 June referendum.
Asked about the US president, the London mayor said everything about the history of the US suggested they would never share sovereignty.
"I don't know what he is going to say but, if that is the American argument then it is nakedly hypocritical. The Americans would never dream of it," he told the BBC.
"I think that President Obama has got a perfect right to make any intervention that he wants. Indeed I welcome the views of everybody in this debate.
"I just find it absolutely bizarre that we are being lectured by the Americans about giving up our sovereignty and giving up control when the Americans won't even sign up to the international convention on the law of the seas, let alone the International Criminal Court."
Labour MP Stephen Kinnock dismissed Mr Johnson's comments as "utter nonsense".
"The last time I checked, the United States was a member of Nato. You look at article five of Nato, it says any attack on a Nato member is an attack on all. You couldn't have a greater pooling of sovereignty than that," he said.
"The United States is a member of the WTO [World Trade Organization] and a range of other international organisations. We pool our sovereignty in order to make ourselves stronger."
By Laura Kuenssberg, BBC political editor
Boris Johnson could hardly be more dismissive of the arguments being put forward by the prime minister, the IMF, the Bank of England, Nato and the White House.
The mayor of London said economic concerns about leaving the EU were fundamentally wrong and he claimed the union was corrupt.
And he said that President Obama's likely warnings about departure would be nakedly hypocritical.
Remain campaign sources say those arguing to leave can't answer basic questions about the economic risks and can't attract the backing of any third parties of any stature.
When pressed for endorsements to rival the In camp, the mayor of London stumbled.
Yet Mr Johnson described his colleagues who want to stay in the union of being the Gerald Ratners of British politics. They believe the EU is "crap" - his word - but say there is no alternative.
Maybe his plain speaking is the passion of the newly converted.
But with Boris Johnson as one of the Leave campaign's biggest voices, if they lose, it won't be for fear of being bold.
Liberal Democrat MP Tom Brake said: "The real issue here is that it's actually Boris Johnson who has been nakedly hypocritical on this issue because of course in January [he] was saying that he actually wanted us to stay in [the EU].
"I think what Boris Johnson has done is made a calculation about him being the future leader of the Conservative Party rather than his views on whether we are stronger in Europe or out of it."
Mr Johnson also reiterated his view that Mr Cameron should stay on as prime minister even if voters backed leaving.
At a rally for the Leave campaign in Newcastle on Saturday, Mr Johnson said the referendum was "a massive opportunity to... burst out of the shackles of Brussels".
The London mayor was applauded when he spoke of the EU being "deeply anti-democratic" and "sometimes borderline corrupt" in how it allocated its budget.
And he said Britain would "thrive and flourish as never before" if it left the EU and agreed its own free trade deals.
EU referendum: In depth
Pro-European Conservative MP Ken Clarke has, meanwhile, predicted Mr Cameron "wouldn't last 30 seconds" as prime minister if the public votes to leave the EU.
He told BBC Radio 4's The Week in Westminster: "We'd be plunged into a Conservative leadership crisis which is never a very edifying sight."
Mr Cameron "would be in a farcical position having campaigned for a position that's been rejected.
"He'd be a prime minister facing a Parliament in which the majority of the MPs wanted to remain in the EU."
BBC political correspondent Ben Wright said Mr Clarke was speaking a truth that many Tory MPs privately acknowledge.
But Mr Johnson said Mr Clarke's comments were "uncommonly pessimistic".
He said Mr Cameron would be in a "strong position" to lead post-referendum negotiations and there were no previous examples of European leaders who had been forced to step down after suffering "adverse referendum results".
"Obviously David Cameron should remain in place," he said.