Making his traditional, and brief, appearance at the Scottish Conservative reception, the Prime Minister made clear that the Tories in the heart of England were passionate for Scotland to remain part of the UK.
Mr Cameron, whose Government has already published several anti-independence analysis papers, boasted that "so far the arguments have been going our way" but warned against complacency.
"All the evidence stacks up so strongly on keeping our United Kingdom together," he declared. "When we look at the arguments about the economy, trade, our currency, the jobs in defence, financial services industry, our relations in the world, our membership of Nato, the EU, the G8, the G7, the G20, the UN Security Council, I'm in absolutely no doubt Scotland together with the UK will be better off, stronger and safer."
But noting how all these were practical issues that appealed to the head, the PM wanted to make a more emotional plea that countered the patriotic pull made by the Scottish Nationalists.
He said: "I want the message to go out from this conference here in Manchester, in England, among the Conservatives, to people in Scotland: we want you to stay, we value Scotland as part of the United Kingdom.
"Yes, Scotland will be better off inside the UK, but I want the rest of the UK to shout loudly and proudly that we will be better off with you with us.
"That is what this debate needs to be about: our common future; the fact that our countries will be so much stronger if we stick together."
Mr Cameron stressed: "I will do everything I can as Prime Minister and leader of the Conservatives to keep the UK together."
Earlier, he mocked Alex Salmond over the First Minister's demand that the PM engage in a live head-to-head debate on St Andrew's Day.
Delegates laughed as he told them: "I seem to have got a new pen pal, writing me letters on an almost daily basis. The letters are really quite like what my children keep saying to me, which is, can we have some time on the telly?
"I've got a message for Alex Salmond, which is this: I know you want to change the subject; I know you want to find some way of deflecting what the real question is."
Mr Cameron said Mr Salmond wanted to turn the debate into one between Scotland and England, between the Tories and the SNP "and we have to tell him no".
"This is a debate between people who live in Scotland and it's about their choice on whether to stay in the UK or leave the UK.
"That is the question and he can try as hard as he likes to try to change the debate but he has to focus on the question in hand," added the Prime Minister, whose keynote address will have a focus on the "absolutely vital battle in keeping our United Kingdom together".
Annabelle Ewing for the SNP said: "David Cameron's position is getting even more ridiculous. He says he will do everything he can to stop Scottish independence but is not prepared to actually debate the issue, even though his Tory Government is driving and directing the No campaign."
She added: "Mr Cameron should either put up or shut up."