The famed Hungarian-American financier has funnelled tens of millions of dollars into left-wing causes around the world, including pro-refugee groups tied to the European migrant crisis and anti-police riots in the US.
In February last year it was revealed the billionaire's Open Society Foundations had pumped hundreds of thousands of pounds into a campaign looking to sabotage British voters' 2016 decision to leave the EU.
He has repeatedly clashed with euroskeptic governments, notably the hard-line Central European Visegrád Group of the Czech Republic, Poland, Slovakia and his native Hungary, which has accused the non-government organisations backed by Soros as operating "like a mafia".
But he said there was a growing threat from anti-EU parties within the bloc's biggest countries including Germany, the UK and Italy.
Writing in The Guardian, Soros lamented the "outdated party system in most European countries" and the "lack of legal tools for disciplining member states that violate the principles on which the EU was founded".
The "antiquated party structure" preventing the "popular will from finding proper expression" was evident in the UK, he said, where both Labour and the Conservatives are "internally divided" on the issue.
He said chances that Prime Minister Theresa May's widely panned Brexit deal would again be rejected were "growing by the day", which could "set in motion a groundswell of support for a referendum — or, even better, for revoking Britain's article 50 notification".
Britain is scheduled to leave the EU on March 29, but Ms May's chief negotiator was overhead in a Brussels bar on Monday night suggesting that date would be pushed back unless MPs vote for her deal next month.
Regarding Italy, Soros said the EU had made a "fatal mistake" in 2017 by strictly enforcing the Dublin agreement, which requires asylum applications to be processed in the first country the person arrives in.
"This drove (Italy's) predominantly pro-European and pro-immigration electorate into the arms of the anti-European League party and Five Star Movement in last year's election," he said.
The country's new hard-line deputy leader Matteo Salvini has taken a zero-tolerance approach, refusing to let NGO ships ferrying migrants across the Mediterranean dock at Italian ports.
Soros said Italy's previously dominant Democratic party was in disarray, leaving many pro-European voters with no party to vote for. He said the situation with trans-European alliances was "even worse".
The European People's Party, the largest party in the European parliament with 215 out of 751 seats, was "almost entirely devoid of principles, as demonstrated by its willingness to embrace Hungarian prime minister Viktor Orbán's Fidesz party in order to preserve its majority and control the allocation of top EU jobs".
"Anti-European forces may look good in comparison: at least they have some principles, even if they are odious," he said. "The current leadership is reminiscent of the politburo when the Soviet Union collapsed — continuing to issue edicts as if they were still relevant."
Soros added it was "difficult to see how the pro-EU parties can emerge victorious from the May elections unless they put Europe's interests ahead of their own".
"The first step to defending Europe from its enemies, both internal and external, is to recognise the magnitude of the threat they present," he said.
"The second is to awaken the sleeping pro-European majority and mobilise it to defend the values on which the EU was founded. Otherwise, the dream of a united Europe could become a 21st-century nightmare."
