In a strongly-worded intervention days before British Prime Minister David Cameron delivers his most important speech on Europe, Britain's closest ally said it needed London to retain a "strong voice" within the EU.
"We have a growing relationship with the EU as an institution, which has an increasing voice in the world, and we want to see a strong British voice in that EU," Philip H. Gordon, assistant secretary of state for European and Eurasian Affairs, told reporters at a briefing in London.
"That is in America's interests," he said, according to two journalists present.
"More than most others, its [Britain's] voice within the European Union is essential and critical to the United States."
US officials have made similar warnings in private in recent weeks, but it was the first time a named senior member of Obama's government had spoken on the record about the risks posed by Britain's debate about its EU future.
Britain's fraught relations with Europe have climbed to the top of the political agenda in recent months, with rebellious anti-EU members of Cameron's ruling Conservatives demanding a new UK role inside the bloc or a referendum on whether Britain should leave altogether.
Urging Britain and the EU to focus on issues such as growth and jobs rather than on the EU's internal workings, Gordon said "referendums have often turned countries inward".
"It is best for everyone, we think, when leaders have the time to be able to focus on common challenges rather than spending their time on internal workings," Gordon said.
"The more the EU reflects on its internal debate, the less it is able to be unified."
Some UK eurosceptics argue that if Britain turned its back on the EU, its biggest trading partner, it could compensate by forging closer ties with the United States.
British business leaders warned earlier on Wednesday that a UK exit from Europe would leave it outside a possible future free trade deal between the EU and the United States.
Cameron, who wants Britain to stay inside Europe, has said the euro zone's debt crisis will change the bloc's rules and means London must redefine its relations with Brussels.
The British leader is widely expected to use his Europe speech in the coming days to announce plans for a referendum on Britain's new EU role. His opponents say that could push London towards the EU exit door.
A spokeswoman for Cameron's Downing Street office said: "The US wants an outward-looking EU with Britain in it, and so do we."
The opposition Labour Party's foreign affairs spokesman Douglas Alexander said the US comments and the warning from British business leaders raised concerns about Britain's role in Europe.
"There is today a real risk of Britain sleepwalking towards exit because of a prime minister motivated more by the need for party unity than by the interests of the country," he said.