Liberal Democrat Alistair Carmichael said September's ballot will be a now or never moment for the Yes side, as further devolution and long-term social changes would make another referendum on independence highly unlikely. He said young voters were increasingly internationalist in outlook because of new technology and social media, and so national borders would be less important in future.
Speaking to the Sunday Herald, the Orkney and Shetland MP also denounced Conservative attacks on the Labour leader of the Better Together campaign as "self-inflicted and utterly unhelpful".
He said recent anonymous briefings against Alistair Darling were frustrating, unnecessary and helped the opposition. Carmichael said: "It offers the Nationalists an opportunity to talk about the process and the campaigning rather than the issues. Our strength in this whole debate lies in the fact that the force of argument on the economy, on the currency, on European Union membership, on pensions, is overwhelmingly on our side."
Although the Yes side has said the Unionist parties cannot be trusted to give Holyrood more powers after a No vote, Carmichael said substantial reforms, including new tax powers for Edinburgh, were in Westminster's self-interest.
Rather than a "neverendum" - where a No vote only led to further ballots - he said a No vote could prove a so-called "neveragaindum", in which the independence issue was permanently settled.
Carmichael said Westminster had learned the lesson of Quebec, where botched reforms led to a second ballot on independence 15 years after the Canadian province rejected the option.
"I think we have the opportunity to settle it [the independence debate]," he said. "First of all, we are able to say with some confidence that there will be an ongoing process of reform which will give more powers to the Scottish Parliament, and that will be delivered on.
"Secondly, I think the generation that is coming through now, the 16 to 24-year-olds, are overwhelmingly opposed to independence. They just see it as being something that is not relevant to their life experience.
"That's a social trend you see which is being given to us by technology. Having had economic globalisation, we've now got a social globalisation.
"They've got Skype, they've got Facebook, they've got Twitter. The concept of putting up boundaries is anathema to that generation. And that's why overwhelmingly they're just not interested in independence."
On the subject of reforms, he said: "In order to complete the devolution project you need to have substantial tax-raising powers for the Scottish Parliament."
However, he said that, although LibDem, Labour and Tory party thinking on more powers would be published before the referendum, there would be no common plan put before voters - partly because the parties wanted people to focus on the Yes/No choice on independence, but also because previous devolution packages had been drawn up with civic society after wide debate, as with the Constitutional Convention of the 1990s and the recent Calman Commission.
Looking ahead to the last four months of the campaign, he predicted a "more intense and more emotional feel to the campaign", but "no massive sea change" in the No camp's approach, with a focus on the economic benefits of the Union.
And he said politicians of all parties had to make sure the passions roused by the referendum did not leave behind a bitter, divided Scotland.
Blair Jenkins, chief executive of Yes Scotland, said: "We are fully focused on winning a Yes vote on September 18 … we are confident that [our] positive, optimistic message will win out over the negativity of the No campaign."