"A clear victory, well done!" said Renzi on Twitter, while jibing at his rivals fighting a series of reforms aimed at boosting growth in the eurozone's third largest economy that while they were "chatting", "we in the meantime are changing Italy".
In Sunday's elections the Emilia Romagna region, traditionally a stronghold of the left, saw the Democratic Party (PD) win 49.6 percent of the vote.
But turnout was just 37.6 percent, compared to over 60 percent at the previous election and there were gains for the anti-immigration Northern League.
In the southern region of Calabria, the PD won with 61.4 percent, with a turnout of 44.1 percent.
"Bad turnout, good results. A clear 2-0. 4 regions out of 4 taken from the centre-right in 9 months," Renzi said on Twitter, referring to two other regional elections his party has won since he came to office in February.
Male affluenza, bene risultati: 2-0 netto. 4 regioni su 4 strappate alla dx in 9 mesi. Lega asfalta forza Italia e Grillo. Pd sopra il 40%.— Matteo Renzi (@matteorenzi) November 24, 2014
The elections saw the anti-establishment Five Star Movement (M5S), led by former comedian Beppe Grillo, take a big hit.
The movement surfed a wave of anti-European sentiment to take a quarter of votes at the general election in 2013. But in Emilia Romagna it secured just 13.3 percent, and just 5.0 percent in Calabria.
Renzi has promised to revive Italy after years of economic recession but has met increasing resistance from trade unions and the Northern League's gain in Emilia Romagna will be seen as a warning sign.
The Northern League, whose head Matteo Salvini is promoting himself as an alternative to Renzi, took home 19.4 percent of the vote, over double the figure secured by ex-premier Silvio Berlusconi's centre-right Forza Italia (FI) party.
The party did not have a candidate running in Calabria, but Salvini has recently outlined ambitions to expand the League's reach into the south, where he hopes to fill the gap left by the ageing billionaire Berlusconi, whose political influence has waned.
"Renzi's balloon is deflating, the League is soaring. Our community is growing everywhere," Salvini said in a tweet.
"We will not stop. We will create an alternative to Renzi across Italy," he said.