Centre-left candidates claimed the upper hand in the 11 provincial capitals up for grabs in weekend runoffs, including in traditional right-wing bastions.
The most spectacular result came in Rome, where right-wing mayor Gianni Alemanno lost his re-election bid to little known challenger Ignazio Marino.
Marino, the candidate of the Democratic Party (PD), romped to victory with 63.9 percent of the vote.
Alemanno conceded defeat, saying the results in city races across the country for his People of Freedom party (PDL) led by former prime minister Silvio Berlusconi were "not positive".
He blamed the losses on Italians' "disaffection" with politics, as barely 45 percent of the electorate cast a ballot in the capital.
Such a figure is exceptionally low for a country accustomed to turnouts of up to 70 percent. The nationwide turnout stood at 48.6 percent.
Marino, a 57-year-old surgeon, spoke to a group of supporters gathered on the central Piazza di Pietra Monday evening, and promised "a new method" based on merit for running the city.
Rome's former mayor Walter Veltroni said however that Marino's win was "excellent news for the city".
"The Romans' vote finally ends five years of indifference and the mistakes that Alemanno and his team committed through incompetence, lack of love (for the city) and personal interests," he said.
The Italian left controlled the Eternal City for nearly 20 years, from 1989 to 2008, when Alemanno, a former neo-fascist, was elected mayor on a strong anti-crime platform.
Results seemed to show a clear advantage for PD candidates in most of the some 60 cities and towns where run-off votes were held Sunday and Monday.
Among those changing hands are central Siena and two northern cities, Brescia and Treviso, which had been held by the anti-immigrant Northern League.
Victory for Marino offers a shot in the arm for the PD, which lost ground in this year's inconclusive general elections, and new misery for the PDL, which also fared poorly in previous recent municipal votes.
The two parties formed an unwieldy coalition government in April after weeks of post-election uncertainty.
The sharp drop in voter turnout over the weekend was seen as reflecting voters' disaffection with politics after the impasse resulting from February's polls.
"It's not a drop, it's a collapse (in voter participation)," the leading Corriere della Sera daily said in an editorial. "This is disenchantment."
Sociologist Piergiorgio Corbetta, writing in the Rome daily Il Messagero, sees the low turnout as an "alarm signal (that) politicians continue to ignore."
But analyst Antonio Noto of the IPR Marketing polling institute blamed the low turnout on the economic crisis.
"The numbers show that local administrators including mayors are losing sway because of the crisis. Lacking financial means, they cannot carry out repairs or improve services," he told the left-leaning daily La Repubblica.
The Five Star Movement of populist firebrand Beppe Grillo meanwhile suffered a rout in the city polls after riding a wave of discontent with politics as usual to win more than 25 percent of the vote in the February general elections.
None of its candidates scored better than third place in the first-round vote in 563 towns and cities, so they were absent from the runoffs.
Analysts say Grillo's relentless attacks on Italy's governance have destabilized the movement. Last week the former comedian described parliament as a "smelly tomb, good for nothing".