He called for unity in an address to the party's Scottish conference in Aberdeen.
Voters decide Scotland's constitutional future on September 18, and there is also the prospect of a vote on Britain's place in Europe.
Mr Clegg, the Deputy Prime Minister, said Westminster or Brussels are not perfect but warned against "isolation" as a response.
He compared the leaders of the two nationalist campaigns - SNP leader Alex Salmond and Ukip leader Nigel Farage.
"I'm not going to claim that the SNP and Ukip are the same, obviously there are very big differences," he told delegates at the Aberdeen Exhibition and Conference Centre.
"But they do both want to bring an end to a partnership between nations that has been forged over time and serves us well, and they both represent the same impulse: to pull away, to break apart.
"Nigel Farage talks about wanting to cause a political earthquake, and the metaphor is apt because there is a clear fault line emerging in British politics today.
"Either you believe that in an uncertain world, we have strength in numbers, as our party believes. Or you think - mistakenly in my opinion - that countries can stand alone and still stand just as tall.
"It's seductive to some, there's no doubt about it: breast-beating nationalism always is. But leading a nation is about responding to the world as it is, not as we might like it to be."
Mr Clegg went head to head with Mr Farage in a televised debate on Europe this week, with a snap poll suggesting the Ukip leader won the argument.
Polls are also getting closer on Scottish independence, with the most recent survey suggesting 42% of people north of the border will vote Yes in six months.
Mr Clegg conceded: "Of course the UK isn't perfect. Nor is Westminster, nor is Brussels. Institutions, alliances, unions - by their very nature they are living, evolving things, in perpetual need of reform.
"But the response to imperfection is not isolation.
"And the United Kingdom is still the fastest growing economy in the G7. It has clout at the negotiating table, credibility with the markets. We are a leading nation in Europe, an economic superpower - something I am going to fight to defend. And by staying together we can continue to pool our strengths and achieve even more."
The Lib Dems argue for a federal set up in the UK, or "home rule", for Scotland.
Mr Clegg said a No vote in September will be a huge opportunity to enhance devolution.
The main unionist parties at Westminster are coming closer to "consensus" on what those extra powers may be, he suggested.
But others in the party warn that a No vote may not be certain.
Former Scottish party leader Tavish Scott told a fringe meeting at the conference that Labour must do more to capture voters in urban parts of central Scotland. He also said Better Together leader Alistair Darling, the former chancellor, cannot reach those people alone.
Mr Scott said: "I don't think Alistair Darling is pulling that whole swathe of people back into definitely voting for the union."
The deputy prime minister said the referendum is about capturing imaginations.
"Just as it is right that we explain the risks and consequences of Scotland voting to exit the union, we must also set out the opportunities of voting to stay," he said.
"The prospect of remaining in the UK must be just as thrilling as the drama of leaving it.
"So let me be absolutely unequivocal: rejecting independence will not be choosing the status quo."
He called for unity in Europe.
"The Liberal Democrats are the only party that is speaking up for the UK's strong position at the heart of the EU," he said.
"We are doing so for the sake of our shared prosperity, our global influence - and to keep our nations open and engaged in the world."
Mr Clegg continued: "Unity, togetherness, openness - these are what matter now, within our family of nations, in our relationship with our European neighbours.
"And we have to keep fighting for them because they are genuinely under threat.
"So, Liberal Democrats, we will expose the temptations of introversion and division wherever we find them.
"We will give people a reason to resist the lure of false patriotism wherever it rears its head.
"We will provide a positive vision for a prosperous future, filled with possibility for every part of the UK.
"Britain is at its best when we are united, when we stand tall in our own backyard, when we are open, outward-facing and engaged, and that is the Britain we will protect."
Mr Clegg had earlier issued a direct plea to those in his own party who say they will back Scottish independence.
The Yes Scotland campaign revealed this week that it has the support of former Scottish Lib Dem chief executive Andy Myles and former party treasurer Denis Robertson Sullivan.
Speaking before the conference address, Mr Clegg said: "I think they're wrong. They are completely wrong.
"If they think that Liberal values, progressive values, are being served by yanking Scotland out of the UK, putting Scotland at the back of the queue in Europe, having to create a new currency from scratch, having to face all the economic consequences which would flow, when there is a positive Liberal vision of further devolution to Scotland within the United Kingdom - then they're flatly, plainly, totally wrong."
He singled out the Scottish Government's proposal to form a currency union with the rest of the UK if there is a Yes vote.
The proposal has already been rejected by Chancellor George Osborne and other UK party leaders.
Mr Clegg said: "People can believe that the moon is made of cheese if they wish, but it's not.
"In the same way, Alex Salmond can claim that he will retain the currency union - he will not be able to. It is simply not going to happen, it is not on offer.
"I do not think it is right for Alex Salmond to claim that the world is flat when it is round, to claim that down is up, and to somehow invite people to believe in commitments that he cannot and will not deliver.
"He will not deliver a currency union because it is not on offer."