The Springfield Mafia is an Italian-American Mafia crime syndicate based in Springfield. The premier family among the Springfield Mafia is the D'Amico Crime Family. Springfield Mafia members include Don Vittorio D'Amico, Marion Anthony "Fat Tony" D'Amico,  Michael D'Amico, Legs, Louie, Johnny Tightlips, Frankie the Squealer, Jimmy the Snitch, Joey, Nicky Bluepants Altosaxophony, and on specific occasions Bart Simpson and Homer Simpson. Like real Mafia, they control various corrupt businesses, discreetly perform unsavory tasks for individuals in exchange for heavy payments that they are very aggressive in later collecting, and battle and frequently kill their enemies, who are mostly law enforcers and other criminals. The Springfield Mafia often non–lethally punish people for minor, petty things. For instance, when Homer ended up borrowing money from Fat Tony and losing it in a football game, Fat Tony hammered down a payment plan by having Louie hammer Homer's hand (using two hammers if he mentioned Professor Pigskin).

Notable episodes featuring the Mafia include "Bart the Murderer", where Bart inadvertently stumbles upon the mob's hideout and is forced to become their bartender, and later is thought to have caused Principal Skinner to be killed by the mob (which turned out to be a misunderstanding), "The Twisted World of Marge Simpson", where Homer hires them to help with Marge's pretzel business and destroy her competitor's business, and when they return to collect their payment, they get into a fight with the Yakuza which the said rivals of Marge had also hired, and "The Mook, the Chef, the Wife and Her Homer", where Lisa makes friends with Fat Tony's son Michael, leading to the Simpsons again becoming involved with the Mafia. When Fat Tony is injured in an attack by a rival family, the Calabreses, and Homer briefly becomes the acting leader. Later, the Calabreses come to the Simpsons' house for dinner, and are poisoned and killed by Michael.

In the recent episode "Donnie Fatso", Fat Tony dies of a heart attack and is replaced as leader of the mob by his cousin "Fit Tony", who as his name implies is much leaner and handsomer than Fat Tony. However, due to the new pressure of running the mob Fit Tony soon gains a lot of weight, and becomes identical to the original Fat Tony, making it as if nothing had happened.