Ahead of a landmark speech by David Cameron on the UK's relationship with Brussels, the US assistant secretary for European affairs made clear 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". Mr Johnson is also among those who have called for a referendum on the EU, something Mr Cameron is expected to promise for after 2015 in his forthcoming speech.
Mr 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.