- Clive Owen as Mr. Smith
- Paul Giamatti as Karl Hertz
- Monica Bellucci as Donna "D.Q." Quintano
- Stephen McHattie as Hammerson
- Greg Bryk as The "Go-to-Guy"
- Daniel Pilon as Senator Harry Rutledge
- Sidney Mende-Gibson as Baby Oliver
- Lucas Mende-Gibson as Baby Oliver
- Kaylyn Yellowlees as Baby Oliver
- Ramona Pringle as Baby's Mother
- Julian Richings as Hertz's Driver
- Jason Reso as Senator's Guard
- Tony Munch as Man Who Rides Shotgun
- Scott McCord as Man who got shot
Smith (Clive Owen), a drifter at a bus stop, sees a pregnant woman fleeing a hitman. Following them into a warehouse, Smith murders the hitman with a carrot and saves the woman. As more thugs arrive, Smith is forced to deliver the woman's baby (later named Oliver) during a firefight. Pursued by head assassin Karl Hertz (Paul Giamatti), the woman is soon shot and killed, forcing Smith to narrowly escape with Oliver.
Leaving the baby in a park, Smith hopes someone will adopt the child, only for a passing woman to be killed by Hertz. Realizing Hertz is trying to kill Oliver, Smith saves him, and attempts to leave him with a lactating prostitute named Donna (Monica Bellucci); despite his pleas, she refuses. Hertz arrives at the brothel shortly after and tortures Donna for information, only for Smith to return and kill Hertz's henchmen.
Taking Donna to his hideout, Smith realizes that Oliver stops crying when he hears heavy metal music, leading him to conclude his mother lived near a heavy metal club. Followed by Hertz, Smith is then forced to shoot his way out of his hideout, before he and Donna head to a nearby club. Heading above the club, they discover an apartment containing medical equipment and two dead pregnant women; Smith concludes the women were all impregnated with a specific man's sperm so they could birth matching bone marrow donors.
Hiding in a motel room, Smith and Donna are attacked by masked men during sex, forcing Smith to kill them while supporting Donna (apparently without her even being aware of the gunplay). Discovering his assailants' weapons are all "Hammerson" models unavailable to the public, Smith takes Donna and Oliver to a war museum, and hides them in a M24 Chaffee armored tank. Infiltrating the Hammerson factory, Smith witnesses Hertz and Hammerson in conversation about how they do not want the Second Amendment repealed by the next President, and notices Hammerson owns a German Shepherdcalled Duchess. Smith booby-traps the entire facility, allowing him to kill his assailants and escape.
Smith soon notices an article on Senator Harry Rutledge (Daniel Pilon), a presidential candidate campaigning for stricter gun laws. Smith deduces Rutledge has cancer and requires a bone marrow transplant, which is why he had surrogates impregnated with his sperm, and why Hertz and Hammerson want Oliver dead; should the infants die, the Senator will not receive a donation and will be unfit to run as President. Smith tells Donna to leave town, before Smith contacts one of Rutledge's henchmen to request an appointment. Meeting aboard a plane, the Senator confirms Smith's suspicions, only for Smith to notice dog hair on his trousers.
Discerning the hair belongs to Duchess, and that the Senator struck a deal with Hammerson, Smith takes Rutledge hostage, only for Hertz and Hammerson to appear. Escaping from Hertz, Smith kills the Senator and leaps from the aircraft with a parachute. Killing several pursuing henchmen, Smith is shot and, after safely landing, soon collapses due to his injuries. Smith subsequently awakes in Hammerson's mansion. Hertz tortures Smith, breaking his fingers to learn where he sent Donna and Oliver. As Hertz prepares to cut Smith's eyes, Smith manages to break free and kill several thugs. Cornered and struggling to use his gun, Smith places live rounds between his broken fingers and, by detonating them using a fireplace, shoots and critically wounds Hertz. As Smith and Hertz both grab pistols and struggle to kill each other, Smith manages to fire first and kill Hertz.
Boarding a bus with Duchess, Smith soon stops at an ice-cream parlor, only to find Donna working as a waitress while watching Oliver. The film ends as a group of amateur robbers enter the parlor; his hands in bandages, Smith shoots them by using a carrot to pull the trigger.
