Speaking in Brussels on Tuesday, the Liberal Democrat MP also said he was surprised that 48 per cent voted to remain in the EU in last June's referendum.
"Given the forces against it and the decades of anti-EU rhetoric, it's amazing so many voted to stay in," he said.
Clegg, who with former Prime Minister David Cameron led a coalition government in the UK,, spoke of the "real risks and dangers" posed by a "wave" of populism and nationalism which he said had now spread from the Kremlin, through parts of Europe, including "the more extreme Brexiteers" and, under US President Donald Trump, to the White House.
"It is what I would call an axis of aggressive nationalism and it has to be stopped," said Clegg.
He said, "It is important to realise that these people, including Nigel Farage, are united by their absolute loathing of all supra-national institutions and arrangements."
Describing this as an "assault" on international governance, he said its "very powerful narrative" had attracted widespread support, as was seen by the Brexit vote and Trump's rise to power.
"It is also important to see this for what it is - a staunch and stark attack on the founding principles of EU integration by forces who want to see the EU unwound altogether."
Clegg also warned that such forces were "heading to political and ideological conflict" with those such as himself who defend the EU.
Clegg, who served as an MEP for five years, warned that the EU was on the "frontline" against this "axis of nationalism", adding, "It would be a big mistake for Brussels to think it all it need do now is defend the battlements of the EU, muddle through and that all will be well."
He continued, "If it thinks that, and this is the first time I have thought this, then I really do fear it could spell the end of the EU itself."
The "only way" the EU27 can defend itself is through reform and by strengthening the bloc, Clegg argued.
Reforms, he suggested, should include a "complete" fiscal union and changes to the rules on the free movement of people, including an "emergency brake" on migration where necessary.
He also said it was vital that EU members "pay their full share" towards the cost of Europe's security and defence, saying this was the one area where he was in "half agreement" with Donald Trump.
"It is clearly unsustainable for Nato members not to pay their fair share in defence and security."
Clegg, who was speaking at a debate, 'What does Europe mean to Europe', organised by Forum Europe, also called on Europe's political elites to "develop the backbone to defend the EU."
He said, "I do not think people have woken up to the absolute earthquake that has occurred on this continent. For many years, the US has sponsored EU integration and now we have a President who believes in the opposite and has called Nato obsolete."
"This is a profound change and I hope that those in London, Berlin and Brussels will wake up to that fact very soon."