Police made 51 arrests in Ostia, a coastal community on the outskirts of the capital, for alleged crimes connected to the Sicilian Mafia, known as Cosa Nostra, police said in a statement.
An additional 65 people were detained in a separate operation in Calabria, where those arrested are suspected of links to the powerful 'Ndrangheta Mafia.
The operation in Ostia is one of the largest ever carried out against organized crime in the Rome area, a police news release said.
More than 500 police officers, as well as maritime and dog units, were involved, police said.
The alleged crimes under investigation in Ostia range from extortion to murder, to international drug trafficking to illegally controlling the slot machine market and business activities related to the beach, police said.
Police say their operation has delivered a "mortal blow" to the leadership of the Mafia organization in the capital.
Entire Mafia clans have been hit by the arrests, they say. Among those detained are alleged Mafia boss Carmine Fasciani.
Members of another Mafia clan, Vincenzo Triassi and his wife, have been arrested on the Spanish island of Tenerife thanks to coordination with Interpol, another police statement said.
They are being held in a Spanish jail awaiting extradition proceedings, police said.
Politicians, businessman, lawyers, doctors and even members of the prison police were arrested in the second operation, which targeted Mafia leadership around Lamezia Terme, a city in Calabria, another police news release said.
Those arrested are accused of crimes including murder, criminal association and extortion, it said.
Every year, the release said, the criminal gang made millions of euros through a system of insurance fraud, with the funds used to finance the acquisition of arms and drugs.
"We are particularly satisfied with the investigation," Rodolfo Ruperti, police chief of the city of Catanzaro, whose force carried out the Lamezia Terme operation, told CNN by telephone.
He said the inquiry shone a spotlight on the "gray area" of relations among politicians, businessmen and Mafia groups suspected of carrying out dozens of murders in past years.