Authorities say 110 of the 127 people facing charges have already been arrested, and the rest are expected by the end of the day. The arrests were being made by FBI agents, working with US Marshals, the NYPD and state police.
Most of the arrests were made in Brooklyn, but there were others throughout New York City, New Jersey and New England.
The suspects are reputed members of all five New York mob families. Members of the DeCavalcante family in New Jersey were also arrested. Luigi Manocchio, the reputed head of New England's Patriarca crime family, was arrested Wednesday in Fort Lauderdale, Fla., the U.S. attorney's office in Providence said. A newly unsealed indictment accused him of collecting protection payments from strip club-owners. Also arrested was Thomas Iafrate, who worked as a bookkeeper for strip clubs and set aside money for Manocchio, prosecutors said. Another arrest was made in Italy.
U.S. Attorney General Eric Holder says the charges cover decades worth of offenses, including hits to eliminate perceived rivals, a killing during a botched robbery and a double shooting in a barroom dispute over a spilled drink.
Federal charges include murder, gambling and racketeering.
"Today's arrests and charges mark an important step forward in disrupting La Cosa Nostra's illegal activities," U.S. Attorney General Eric Holder said. "This largest single-day operation against La Cosa Nostra sends the message that our fight against traditional organized crime is strong, and our commitment is unwavering. As we've seen for decades, mafia operations can negatively impact our economy - not only through a wide array of fraud schemes but also through the illegal imposition of mob "taxes" at our ports, in our construction industries, and on our small businesses."
The takedown was the result of multiple investigations. Federal probes aided by mob turncoats have decimated the families' ranks in recent years and have resulted in lengthy prison terms for several leaders.
On Friday, a federal judge in Brooklyn sentenced John "Sonny" Franzese, 93, to eight years in prison for extorting Manhattan strip clubs and a pizzeria on Long Island.
Federal prosecutors had sought at least 12 years behind bars for the underboss of the Colombo crime family - in effect, a life term. To bolster their argument, they had an FBI agent testify that Franzese bragged about killing 60 people over the years and once contemplated putting out a hit on his own son for becoming a government cooperator.
In October, Mafia turncoat Salvatore Vitale was sentenced to time served after federal prosecutors praised his total betrayal of his own crime syndicate - and after he apologized to the families of his victims. Authorities said he had a hand in at least 11 murders, including that of a fellow gangster in the fallout from the infamous Donnie Brasco case.
The evidence provided after his arrest in 2003 helped decimate the once-fearsome Bonanno organized crime family, Assistant U.S. Attorney Greg Andres said.
"The Mafia today is weaker because of his cooperation," Andres said. "Mr. Vitale provided lead after lead...The results speak for themselves."
(The Associated Press contributed to this report.)