Ahead of a landmark speech by David Cameron on the UK's relationship with Brussels, the US assistant secretary for European affairs made clear on Wednesday that Washington favoured a "strong British voice" within the EU.
Philip Gordon also warned that referendums could turn countries "inward".
"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," he told reporters during a visit to London.
"That is in America's interests. We welcome an outward-looking EU with Britain in it."
The prime minister is due to make a speech this month in which he will set out his plans to renegotiate Britain's relationship with the EU - including clawing back many powers - and put that settlement to voters.
Some in his party advocate British withdrawal, a scenario which Conservative Mayor of London Boris Johnson has said would not be "the end of the world". Johnson is also among those who have called for a referendum on the EU, something Cameron is expected to promise for after 2015 in his forthcoming speech.
Gordon said "referendums have often turned countries inward" and raised concerns about the internal debate in the EU about its structures in the aftermath of the eurozone debt crisis.
"Every hour at a summit spent debating the institutional make-up of the European Union is one hour less spent on how to deal with the common issues of jobs, growth and international peace around the world," he said.
He stressed that he was speaking up for US interests and would not interfere in British decisions. "What is in the UK's interests is up to the UK," he said.
British business leaders also warned of the "uncertainty" that could be created by demands for a new relationship with the EU.
In a letter to the Financial Times, figures including Sir Richard Branson, the head of Virgin, Sir Roger Carr, president of the CBI, and Sir Martin Sorrell, chief executive of the advertising group WPP, cautioned against demands for "a wholesale renegotiation of our EU membership, which would almost certainly be rejected".
"To call for such a move in these circumstances would be to put our membership of the EU at risk and create damaging uncertainty for British business, which are the last things the prime minister would want to do. We need a strong reformed EU with Britain at the heart of it."
Shadow foreign secretary Douglas Alexander said: "On the same day that top British business leaders fired a warning shot across the bows of the prime minister, a senior White House official has also signalled concerns about the possibility of Britain leaving the EU.
"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."
A Number 10 spokesman said: "The US wants an outward-looking EU with Britain in it, and so do we."