The indictment accuses alleged mob leader Joseph "Uncle Joe" Ligambi, reputed underboss Joseph Massimino and the others of running illegal gambling operations or loan sharking.
Eleven of the 13 people charged were arrested early Monday and were due in court for initial appearances in the afternoon, but it was not immediately clear if they had obtained attorneys. The other two defendants were already in federal custody.
The arrests were the largest action taken against Philadelphia's crime family in a decade.
"They used violence and the threat of violence to exert control over others," Assistant Attorney General Lanny Breuer said in a news conference, noting that organized crime in Philadelphia had shown "a remarkable ability to reorganize and reinvent itself."
U.S. Attorney Zane David Memeger said the arrests should serve as a warning to the city's Mafia that law enforcement hasn't forgotten about them.
"Today, we make clear that such activity will not be tolerated by my office and that La Cosa Nostra remains a priority for the Department of Justice," Memeger said.
Ligambi, Massimino and the others provided illegal gambling devices including video poker machines to bars, restaurants and convenience stores in and around Philadelphia, prosecutors said. The group then allegedly forced another illegal gambling ring to sell their business to them after authorities seized their own machines.
Ligambi, 72, took over the Philadelphia mob after former boss Joseph "Skinny Joey" Merlino was convicted of racketeering in 2001, according to investigators. Merlino was later acquitted of a murder charge in 2004.
Ligambi was convicted in the 1985 gangland slaying of Frank "Frankie Flowers" D'Alfonso and spent 10 years in prison before he was acquitted on retrial in 1997.
Merlino is currently serving a six-month term at a Florida halfway house after being released from federal prison in March.
