In Boston, two Irish American twin brothers, Connor and Murphy MacManus, attend Mass, where the priest mentions the fate of Kitty Genovese. Later, when Connor and Murphy are celebrating St. Patrick’s Day with friends, three Russian mobsters arrive and announce they want to close the pub and take over the land it is built on. A brawl ensues, in which the Russians are defeated and humiliated. The next morning, when two of the Russians seek revenge on Connor and Murphy, the mobsters are killed in self-defense.
FBI Agent Paul Smecker is assigned to the case, and finds that the police and local news reporters see the MacManus brothers as heroes. The duo turn themselves in at a police station, where Smecker interviews them. After they retell their incident to Smecker, he declines to press charges and allows them to spend the night in a holding cell to avoid attention from the media. That night, they receive a “calling” from God telling them to hunt down wicked men so that the innocent will flourish.
Connor and Murphy resolve to rid Boston of evil men. Connor learns of a meeting of Russian syndicate bosses at a hotel. Having equipped themselves with weaponry from a local underground gun dealer, the brothers quickly kill all nine Russian mobsters, while Rocco, a friend of the brothers and errand boy for local mafia boss Giuseppe “Papa Joe” Yakavetta, is sent on a hit as an unknowing pawn. The next day, Rocco learns that he was betrayed, having been sent to kill nine Russians with only a six-shot revolver. Rocco commits himself to helping Connor and Murphy. That night, they hunt down and kill Vincenzo Lapazzi, an underboss of the Yakavetta crime family.
Concerned he may be a target, Papa Joe contacts a hitman, Il Duce, to deal with them. After killing a criminal that Rocco had a personal hatred for, the three men are ambushed by Il Duce. Although they manage to chase Il Duce away, the three men suffer serious wounds, including the loss of Rocco’s finger. The three return to a safehouse where they treat their wounds.
Hours later as the police conduct an investigation at the crime scene, the investigation seems futile since the brothers covered their tracks by spraying any blood left behind with ammonia. However, Smecker happens upon the part of the finger lost by Rocco and decides to do an independent investigation to see who was behind the gun battle. Smecker is able to track the evidence down to Rocco and his two allies. This leaves Smecker in a difficult scenario, and struggles with the choice of whether to prosecute the three men, or join them in their cause, as Smecker believes they are doing the right thing. After getting drunk at a gay bar and subsequently getting advice from a reluctant priest, Smecker decides to help the trio.
Later, the brothers and Rocco inform Smecker that they plan to infiltrate the Yakavetta headquarters to finish off the family, but Smecker learns they are walking into a trap. The brothers are captured, and Rocco is shot and killed by Papa Joe, but the brothers are able to free themselves. As Papa Joe leaves his house, Smecker arrives in drag and kills a number of soldiers before being knocked unconscious by Il Duce. As the brothers say their family prayer over Rocco, Il Duce enters the room and prepares to open fire. However, he instead finishes the prayer – revealing he is the brothers’ father and decides to join his sons in their mission.
Three months later, Papa Joe is sent to trial for a third time. However, the reporters on-scene anticipate his acquittal. The brothers and Il Duce, aided by Smecker, Dolly, Duffy and Greenly, infiltrate the trial after sliding their weapons over the metal detector. Unmasked, they make a speech stating that they intend to eradicate evil wherever they find it before reciting their family prayer and killing Papa Joe. The media dubs the three as “the Saints”.