The anti-Renzi factor
Renzi was nicknamed the "demolition man" when he snatched power in 2014 for his reputation for taking on the establishment, but his popularity slipped in the months leading up to the ballot.
His bullish style came to be seen as arrogance, including by some slighted grandees of his own party, and many Italians accused him of being in league with Brussels, fat cats and the banking sector.
"Renzi is strongly disliked," said Antonio Noto, head of IPR Marketing polling institute, adding that votes against the PM were "votes against the establishment, but also against his style".
Cecila Carrara, a lawyer in an international firm, said Renzi's "record is disastrous, he has mainly focused on getting good publicity".
The former mayor of Florence also came under fire for failing to get Europe to share the burden of the migrant crisis. Butcher Antonio Canestri told AFP that when it came down to it, "Europe wasn't listening to Renzi".
Renzi was accused of failing to reboot the country's flagging economy - which has barely grown since 2000 - or tackle the jobless rate, which has been vacillating between 11.4 percent and 11.7 percent for the last 15 months.
A slight dip in the youth unemployment rate to 36.4 percent - its lowest rate since October 2012 - failed to mollify the disaffected.
"Those who voted 'No' were impoverished middle-class families, hit by the economic crisis, without hope of prosperity or well-being for children or grandchildren... (and) the unemployed young," editorialist Maurizio Molinari wrote in La Stampa daily.
Fabrizio Sabelli, professor at the University of Geneva, said "the constitution is not the fundamental problem. It's the improvement of living conditions of so many people who suffer, and this jolt will undoubtedly do us good".
In the areas with the highest jobless rate the "No" camp won with 65.8 percent, while the impoverished south also largely voted "No".
Defending the constitution
Polls ahead of the ballot showed many voters did not understand the constitutional reform.
Others were worried the proposed changes were dangerous for democracy because they would have removed important checks and balances on executive power.
"Renzi is punished from north to south for his decision to personalize the constitution," wrote the left-leaning Il Fatto Quotidiano.
The 1948 charter, drawn up in the wake of the fascist regime, was "written by selected, enlightened people, not like the politicians we now have and who are not up to the task," said Emanuela Carosi, an egg seller in a Roman market.
Massimo Franco, an editorialist for Corriere della Sera, said: "Labelling this a populist victory against the establishment would be reductive... There is a populist imprint but a mix of factors played their parts, from hostility to Renzi to a desire to defend the constitution".