Transatlantic relations must remain strong even if the UK votes to leave the EU, Chris Grayling urged Americans as he took the Brexit campaign to America.
The Commons leader said "the view from Washington" wasn't the way to judge what was in Britain's best interests as he renewed criticism of Barack Obama for publicly backing a Remain vote and urged Americans to stay out of the debate.
"Neither of us should ever be at the back of the line when it comes to working together," he said in a swipe at the US President's warnings over the poor prospects of negotiating a swift bi-lateral trade deal.
And he noted that neither Mr Obama nor any other presidential hopeful would ever have stood a chance of being elected had they proposed a similar arrangement for the Americas.
In a speech on Capitol Hill, Mr Grayling said it was the equivalent of asking American voters to accept being ruled by a parliament in Panama, a supreme court in Venezuela, merging their military into an "army of the Americas" and allowing "every Mexican ... the freedom to move to New York City if they choose".
"Suggesting that the United States should be part of such an organisation does not seem to me to be a political platform likely to command widespread support here," he said.
"But that is exactly where the United Kingdom finds itself today."
He said the introduction of the European single currency "created the economic equivalent of the San Andreas fault" - the geological feature that causes major earthquakes in parts of the US.
And there was no way for the UK to avoid the consequences of the economic and political earthquakes it was causing, he suggested.
"We will have little ability to defend our national interest. We will be outvoted all the time. But more and more of our law-making will be sucked into Brussels," he said.
"We will be of marginal importance while footing a large slice of the bill. The US would never accept that. Why should it expect its closest allies to do so?
"in European terms that really does mean finishing our equivalent of that fictitious American Union – not just with a Parliament in Panama City, but with a single Government of the Americas there as well.
"Europe has no choice but to make its version of that fiction a reality."
David Cameron's renegotiation deal cemented existing opt-outs but "gave us a little extra protection against being sucked into a European superstate", he said.
He concluded: "When Barack Obama visited London in April, he made it very clear that he believes Britain should stay in the EU.
"A number of other US politicians have made a similar arguments. Often they have done so with honest intent and with what they believe to be the best interests of the United Kingdom at heart.
"But the view from Washington isn't really the best way of judging what is right and wrong for the United Kingdom, and I think President Obama was wrong to insert himself into the debate in this way.
"In the same way that the United Kingdom should respect the big decisions taken in the US, so the verdict on the future of the United Kingdom must be one for the people of the UK alone.
"Inside or outside the EU, Britain's relationship with the United States will and must remain strong. Neither of us should ever be at the back of the line when it comes to working together.
"If Britain chooses to leave, our partnerships in defence, in intelligence, in counter-terrorism, in trade and in culture should remain strong and unchanged. Neither of us would benefit from growing apart, and neither of us should want that to happen, regardless of how Britain chooses to shape its future.
"We have a unique and special relationship that has survived changes of Government and changes of circumstance. That relationship will and must stay strong regardless of how the British vote in June. As David Cameron himself has said, I believe our best days together lie ahead.
"And our friends here in Washington and across the United States should understand the challenge we face, and should stand aside as we reach our own best view about how we secure our future."