"The anti-establishment Five Star Movement has made big gains in Italy, winning mayoral races in Rome and Turin, early results show.
PD has secured Italy's financial capital, Milan, and Bologna.
The results could give anti-globalist Five Star a platform for parliamentary elections due in 2018, observers say.
Italy local elections were held in two stages, with a first round a fortnight ago and the second round on Sunday.
Ms Raggi, a 37-year-old lawyer who was little known just a few months ago, was on course to win two-thirds of the vote, defeating the PD candidate, Roberto Giachetti.
"I will be a mayor for all Romans. I will restore legality and transparency to the city's institutions after 20 years of poor governance. With us a new era is opening," she said.
Ms Raggi will find a city mired in debts of more than €13bn (£10bn; $15bn) - twice its annual budget.
Romans are frustrated by potholes, piles of rubbish and serious deficiencies in public transport and housing, the BBC's James Reynolds reports from the Italian capital.
When in Rome shake up the politics
In Turin, another Five Star woman, Chiara Appendino, inflicted an additional blow on the Democratic Party, whose candidate had come out on top in the first round of voting two weeks ago.
Founded by comedian Beppe Grillo in 2009, Five Star has been campaigning against the corruption that has plagued Italian politics for years.
PD's Ignazio Marino resigned as mayor of Rome in October over an expenses scandal. The city has been without a mayor since then.
A much bigger scandal, involving alleged Mafia influence in Rome city hall, has fuelled Five Star's rise.
It is looking to establish itself as the main opposition party in the 2018 general election.
In Naples, Italy's third city, former prosecutor Luigi de Magistris, a centrist, was likely to win a second term.
Prime Minister Renzi has staked his political future on an October referendum in which he wants Italians to back far-reaching constitutional reforms.
The plan is to end Italy's tradition of "revolving-door" governments and inject stability after years of party infighting and legislative logjams."