Millions of people in the wealthy regions of Lombardy and Veneto, both run by the once openly secessionist Lega Nord party, voted more than 90 percent for "yes", according to preliminary results.
Two of Italy's wealthiest northern regions on Sunday voted overwhelmingly in favour of greater autonomy in the latest example of the powerful centrifugal forces reshaping European politics.
Voters in the Veneto region that includes Venice and Lombardy, home to Milan, turned out at the high end of expectations to support the principle of more powers being devolved from Rome in votes that took place against the backdrop of the crisis created by Catalonia's push for independence.
Veneto President Luca Zaia hailed the results, which were delayed slightly by a hacker attack, as an institutional "big bang". But he reiterated that the region's aspirations were not comparable to the secessionist agenda that has provoked a constitutional crisis in Spain.
Turnout was projected at around 58 percent in Veneto, where support for autonomy is stronger, and just over 40 percent in Lombardy. The presidents of both regions said more than 95 percent of voters who had cast ballots had, as expected, done so to support greater autonomy.
The votes are not binding, but they will give the right-wing leaders of the two regions a strong political mandate when they embark on negotiations with the central government on the devolution of powers and tax revenues from Rome.
Unlike Catalonia's October 1 independence referendum, which Spain had declared unlawful, the Italian votes were held in line with the constitution. But they are not binding on Rome.
Lombardy, home to financial hub Milan, accounts for about 20 percent of Italy's economy, which is, in turn, the euro zone's third largest. Veneto, which includes the tourist magnet Venice, accounts for 10 percent.
In both regions, many people complain their taxes are wasted by the central government, accusing Rome of delivering low-quality public services and diverting money to the poor south.
"Lombardy and Veneto have two efficient administrations and public services work well, much better than in other Italian regions ... this is why I think it is worth asking for greater autonomy," said Massimo Piscetta, 49, who voted outside Milan.
Lega Nord was established in the 1990s to campaign for an independent state of "Padania", stretching across Italy's north, from around Lombardy in the west to Venice in the east.
It no longer campaigns for secession and its top leadership is trying to broaden its appeal beyond the north ahead of national elections expected early next year – a goal that could be undermined if the referendums rekindle north-south tensions.
Lega's political opponents say the votes were a waste of time and money, given that the constitution allows regions to enter into negotiations at any time with Rome to take on more functions from the centre.
A growing trend
Secessionist sentiment in Veneto and Lombardy is restricted to fringe groups but analysts see the autonomy drive as reflecting the same cocktail of issues and pressures that resulted in Scotland's narrowly-defeated independence vote, Britain's decision to leave the EU and the Catalan crisis.
"What this vote has shown is that there is no 'autonomy party' in Veneto – what there is, is an entire people who back this idea," said Zaia.
"What's won is the idea that we should be in charge of our own backyard."
Lombardy governor Roberto Maroni said he would be looking to present detailed proposals on devolution within two weeks, in a bid to ensure they are considered before national elections due by May next year.
"I will go to Rome and ask for more powers and resources within a framework of national unity," he said.
Analysts say the northern regions' enthusiasm for autonomy does not represent a threat to the unity of Italy in the short term.
But they do see it being a disruptive force over coming decades, particularly as the heavily indebted central government can ill afford to forego the net contribution it gets from the country's most dynamic areas.