Vito Scaletta (Rick Pasqualone) looks through a photo album as he begins to recount his life story. Born in Sicily in 1925 to an extremely poor family, he and his family emigrate to the fictional city of Empire Bay in America a few years later, but they are no better off there than they were in Sicily.
While in school, Vito gets involved with a local delinquent named Joe Barbaro (Robert Costanzo), who eventually becomes his best friend. Vito is arrested during a botched robbery and given a choice: go to jail or join the Army.
He chooses the latter and is sent to Sicily during World War II, where he serves as a paratrooper in Operation Husky for a further year and a half before being wounded and sent home on leave.
Almost immediately after he returns to Empire Bay, Vito manages to get a hold of counterfeit discharge papers, courtesy of Joe’s mob connections. He also learnt that his late father left his mother and sister in massive debt.
Hoping to make money, Vito turns to Joe, who introduces him to Henry Tomasino (Sonny Marinelli), a made man of the Mafia, working for mob boss Alberto Clemente (Nolan North). Working under Henry, Vito is introduced to a real life of crime and eventually succeeds in paying his father’s debt.
However, Vito is later arrested for illegally distributing ration stamps and sentenced to ten years in prison, where he falls in with a crowd led by Leo Galante (Frank Ashmore), consigliere for another mob boss, Frank Vinci (Larry Kenney).
Meanwhile, Vito’s mother dies sometime during his sister’s visit and all of his leftover money that he meant to give to his sister for her wedding is used for their mother’s funeral instead. Vito is released in April 1951, having gotten nearly four years off his sentence, courtesy of Galante’s connections.
Meeting up with Joe, who now works for the last of Empire Bay′s three mob bosses, Carlo Falcone (André Sogliuzzo), Vito starts doing odd jobs for Falcone, eventually becoming a made man in the Falcone crime family and buying a suburban house.
Vito and Joe′s biggest job comes when they are sent to assassinate Clemente, who ordered the kidnapping of a Falcone′s accountant and influenced Vinci to turn on him as he is going against the commission‘s tradition of opposing drugs.
The assassination doesn’t quite go as planned: Joe’s childhood friend and wannabe gangster Marty Santorelli (Jason Spisak), the getaway driver for the job, is killed by Clemente who, after a lengthy car chase, is killed after being shot multiple times by a grieving Joe.
Soon after, Vito is approached by Henry, who now wants to work for Falcone due to Clemente’s downfall. At Falcone’s behest, Henry is sent to murder Galante, but Vito saves his old friend by convincing Henry to let Galante simply “disappear”. After taking Galante to the train station so he can lay low by leaving Empire Bay, Vito returns home, only to find his sister on his front porch crying about the abuse her husband gives her.
Vito brutally beats him up, threatening to kill him if he doesn’t care for her. Horrified by Vito’s actions, she disowns her brother, severing all ties with him. The following night, an Irish mob, who had feuded with Galante in prison, burns Vito’s house to the ground in belated retaliation for one of their high-ranking members
Vito killed in prison. Penniless, Vito settles on living in Marty’s old apartment for the time being. To help Vito get out of debt, Henry gets him and Joe involved in the drug trade, revealing that Falcone is also involved, but will want a large cut of the profits if he discovers their racket.
Although the trio is successful, the Triads discover that Henry is a federal informant and savagely kill him in the middle of a park in broad daylight. Unaware of Henry’s federal ties, Vito and Joe seek vengeance by shooting up a Chinatown restaurant, killing the man who sold them the heroin in the first place.
Vito and Joe realize they are in serious trouble: with Henry dead and being ousted as an informant, they are soon scrutinized by Falcone for vouching for a “rat”; the gunfight in Chinatown agitated the Triads, who are now preparing for war; with Falcone having taken his cut and the Triads stealing whatever money left from Henry, Vito and Joe must also find a way to repay the $55,000 loan they took from the Jewish loan shark, Bruno Levine.
They manage to re-earn enough money: first, they murder former mobster Tommy Angelo, who turned pentito on his boss Ennio Salieri; Vito learns his father was drowned at the docks on orders of his union boss Derek Pappalardo, Vinci′s caporegime, whom Vito′s mother urged her son to work with earlier in the story. Vito kills Derek and his men, then takes Derek’s retirement money.
Vito daringly surrenders himself to Vinci in hopes that he will be able to find Joe. He does, and together they escape, shooting up the construction site they were being held at. While paying Bruno his money back, Vito discovers Bruno is the very same loan shark who had loaned his deceased father so much money.
The incident in Chinatown has caused great tension between Falcone and Vinci, as each believes the other is responsible, with the incidents at the docks and the construction site furthering problems between the two families. Galante returns to Empire Bay, negotiating a deal with Vinci and the Triads that they spare Vito’s life if he kills Falcone.
Conversely, Falcone offers Joe the position of caporegime if he kills Vito, but Joe betrays Falcone, not wanting to kill his lifelong friend. They succeed in killing Falcone and are picked up by Vinci’s men to celebrate.
But when Joe′s escort makes an unexpected turn, Vito is informed by Galante that the deal didn’t cover Joe. Helpless, Vito watches sadly as Joe is driven away to whatever fate awaits him in exchange for their actions and the game concludes with a panoramic view of Empire Bay.