TURIN, Italy — Italy’s prime minister, Matteo Renzi, only 41, once seemed to have solved the riddle of how to survive Europe’s populist, anti-establishment tempest. But with a critical national referendum on Sunday, the populist wave is now threatening to crush him and plunge Italy into a political crisis when the European Union is already reeling.

From Washington to Brussels to Berlin, fears are rising that Italy may be stumbling into its own “Brexit” moment. What should be an inward-looking referendum on whether to overhaul Italy’s ossified political and electoral system has taken on much broader import. Financial analysts warn of a potential banking crisis, and pro-Europe supporters fear that a “no” vote in the referendum could accelerate the populist movement across the European bloc.

Italy is potentially the next domino to fall, partly because of the disillusionment of young voters. They have been swept up by many of the same forces that led peers in Spain and Greece to vote for upstart parties, the British to vote to leave the European Union, and Americans to elect Donald J. Trump. In France, President François Hollande announced on Thursday that he would not seek re-election — another establishment figure succumbing to the political moment.

Mr. Renzi’s supporters have taken to calling his opponents in the internet-born, populist Five Star Movement “Trumpisti.” They accuse their opponents’ numerous blogs and websites of flooding the Facebook accounts of young people with anti-Renzi, pro-Russian fake news. The referendum has essentially become a referendum on Mr. Renzi, who gave extra motivation to his political enemies by vowing to resign if voters reject the proposed political changes.