The Conservative leader has been under pressure from many of his MPs to give a binding commitment to a vote on Europe.
But Foreign Secretary William Hague told the BBC that Mr Cameron's message was not "confined or directed" to his backbenchers or those voters attracted by the UK Independence Party's call for EU withdrawal and should resonate across Europe
"It is not the Conservative Party he is speaking to. It is the British public and the European public."
Conservative MPs who want a looser relationship with the EU welcomed Mr Cameron's promise and said it had united the party.
One MP, Mark Reckless, even suggested Mr Cameron had left his own position in a referendum "up for grabs" and had the "wriggle room" to campaign for an exit if he believed this was the only option left for Britain.
Labour said Mr Cameron was "going to put Britain through years of uncertainty, and take a huge gamble with our economy".
But their leader Ed Miliband came under pressure himself after he appeared to go further than he has done before and told MPs that he opposed the idea of an in/out referendum.
The opposition have previously declined to rule out a referendum in the future while arguing that now is not the right time for one, but party sources insisted their position had not changed.'Ill-defined'
Lib Dem leader Nick Clegg, who is also deputy prime minister, said there was a "right place and right time" for a referendum.
But he added: "My view is that years and years of uncertainty because of a protracted, ill-defined renegotiation of our place in Europe is not in the national interest because it hits growth and jobs."
The UK Independence Party said the "genie was out of the bottle" about a possible exit from the EU but acknowledged that winning a referendum on a platform for withdrawal would not be easy.
Conservatives have said their reform message is likely to win favour with European allies such as Sweden and the Netherlands.
German Chancellor Angela Merkel said she would listen to British "wishes" but her foreign minister Guido Westerwelle said "cherry picking is not an option" before adding that Europe needed more, not less, integration.
And French foreign minister Laurent Fabius warned: "You can't do Europe a la carte... to take an example which our British friends will understand - imagine Europe is a football club and you join, once you're in it you can't say 'Let's play rugby'".
In response, No 10 said the British public would have the final say.