Voting starts early on Sunday, with the first exit polls expected on Monday morning. But it may fall short of a majority, leaving the populist Five Star Movement (M5S) with an opening to wield significant influence. Renzi was the prime minister of Italy's most recent government, until he stepped down after losing a proposed constitutional reform referendum by a large margin.
The campaigns have been marked by episodes of racism and political violence unseen in Italy since the 1970s, including the shooting of six migrants, an act described by the nationalist perpetrator as revenge for the murder of an Italian woman, allegedly by a migrant.
Renzi's rivals include the populist Five-Star Movement, as well as a coalition of right-wing parties, including the far-right League party, which has been backed by neo-fascists.
Raffaele Fitto, however, another coalition partner, was caught on an open microphone saying Five Star could sweep the south, a must-win region for Berlusconi.
Final rallies were held by the ruling Democratic Party, the anti-establishment Five Star Movement and the anti-immigration Northern League.
Berlusconi, who can not now take up office himself due to a tax fraud conviction, has backed European Parliament President Antonio Tajani to lead the country.
Italy has been a gateway for hundreds of thousands of migrants seeking asylum and opportunities in Europe, but far-right parties promising to be tougher on migration have garnered more support than ever before.