The treasury department said in a statement it was sanctioning Camorra mob boss Marco Di Lauro, fugitive Mario Riccio and three other mobsters.
It was also sanctioning two businesses with ties to the "Brothers Circle" - a multi-national criminal network whose tentacles stretch throughout Europe and the rest of the world.
The moves are "a continuation of our systematic effort to expose and disrupt these dangerous groups and protect the US financial system from their illicit activity," Under Secretary for Terrorism and Financial Intelligence David Cohen said in a statement.
Di Lauro has been on Italy's most wanted list since 2004 for mafia-related activities. Riccio, 22, is tied to a drug-trafficking network that nets "tens of millions of euros" each year, the treasury department said.
It said "The Brothers Circle" was a multi-ethnic group composed of criminals largely from the former Soviet Union but also extending around the world. The US government has already sanctioned 15 people with ties to the organization.
The Treasury sanctions mean the assets of individuals and businesses held in the US have now been frozen. The sanctions also ban any dealings with those involved.