The film begins with the sentencing of Jean-Baptiste Grenouille (Ben Whishaw), a notorious murderer. Between the reading of the sentence and the execution, the story of his life is told in flashback, beginning with his abandonment at birth in a French fish market. Raised in an orphanage, Grenouille grows into a strangely detached boy with a superhuman sense of smell. After growing to maturity as a tanner's apprentice, he makes his first delivery to Paris, where he revels in the new odors. He focuses on a redheaded girl (Karoline Herfurth) selling yellow plums, following her and repeatedly attempting to sniff her, but startles her with his behavior. To prevent her from crying out, he covers the girl's mouth and unintentionally suffocates her. After realizing that she is dead, he strips her body naked and smells her all over, becoming distraught when her scent fades. Afterwards, Grenouille is haunted by the desire to recreate the girl's aroma.
In the late 2020s the world is in turmoil, with the United States fractured as a result of prolonged conflict and a pandemic of the "St. Mary's Virus" ravaging Europe. The United Kingdom is ruled as a fascist police state by the Norsefire Party. Political opponents, immigrants, Muslims, homosexuals and other "undesirables" are imprisoned in concentration camps. On November 4, a Guy Fawkes-masked vigilante identifing himself as "V" (Hugo Weaving) rescues Evey Hammond (Natalie Portman), an employee of the state-run British Television Network (BTN), from members of the "Fingermen" secret police while she is out past curfew. From a rooftop, they watch his demolition of the Old Bailey criminal court building, accompanied by fireworks and the 1812 Overture. Inspector Finch (Stephen Rea), Scotland Yard's Chief of Police, is tasked with investigating V's activities while BTN declares the incident an "emergency demolition". V interrupts the broadcast to claim responsibility and urges the people of Britain to rise up against their government. He asks them to meet him exactly one year later, on November 5, Guy Fawkes Night, outside the Houses of Parliament, which he promises to destroy. During the broadcast, the police attempt to capture V. Evey helps him escape but is knocked unconscious.
Convicted murderer Seth Baxter wakes up chained to a table beneath a pendulum blade. A videotape informs him that he can release himself by crushing his hands between two presses. He does so, but the blade still swings down and cuts him in half as someone watches through a hole in the wall. In the meatpacking plant, FBI Agent Peter Strahm guns down Jeff Denlon and is locked in the sickroom. He discovers a hidden exit with a microcassette recorder, which urges him to stay in the sickroom. He ignores it and is attacked in the tunnel by a pig-masked figure, waking up with his head sealed in a box which quickly fills with water; he survives by performing a tracheotomy using his pen. Outside, Detective Mark Hoffman delivers Corbett Denlon to the police and claims they are the only survivors, and is shocked when Strahm is also brought out alive.
In 1963 Oregon, Randle Patrick "Mac" McMurphy (Jack Nicholson), a recidivist anti-authoritarian criminal serving a short sentence on a prison farm for the statutory rape of a 15-year-old girl, is transferred to a mental institution for evaluation. Although he does not show any overt signs of mental illness, he hopes to avoid hard labor and serve the rest of his sentence in a more relaxed hospital environment.
Child psychologist Catherine Deane (Jennifer Lopez) is an expert in an experimental treatment for coma patients: a virtual reality device that allows her to enter into the minds of her patients and attempt to coax them into consciousness. When serial killer Carl Rudolph Stargher (Vincent D'Onofrio) falls into a coma before the FBI can locate his final victim, Agent Peter Novak (Vince Vaughn) persuades Deane to enter Stargher's mind and discover the victim's location. Stargher's victim is imprisoned in a cell in the form of a glass enclosure that is slowly filling with water by means of an automatic timer.
Adam, a young photographer, awakens in a filthy bathtub. He gets out and finds himself chained to by one foot to a pipe in a large dilapidated bathroom. Lawrence Gordon, an oncologist, is chained by one foot to a pipe across the room and between them lies a corpse, holding a revolver and a microcassette recorder. Adam manages to retrieve the recorder and they learn from tapes in their pockets what they must do: Adam must escape the bathroom, and Lawrence must kill Adam before six o'clock, or his wife and daughter will die and he will be left to die as well. Using a clue from the tape, Adam finds a bag in the toilet tank containing two hacksaws, though neither is able to cut through their chains. Adam's saw breaks and he throws it at a mirror in frustration. Lawrence realizes the saws are meant to be used on their feet and identifies their captor as the Jigsaw Killer, whom Lawrence knows of because he was once a suspect.
After spending eight years in prison for rape, Max Cady (Robert Mitchum) is released. He promptly tracks down Sam Bowden (Gregory Peck), a Georgia lawyer whom he holds personally responsible for his conviction because Sam interrupted his attack and testified against him. Cady begins to stalk and subtly threaten Bowden's family. He kills the Bowden family dog, though Sam cannot prove Cady did it. A friend of Bowden's, police chief Mark Dutton (Martin Balsam), attempts to intervene on Bowden's behalf; but he cannot prove Cady guilty of any crime.
Growing up, Evan Treborn, and his friends, siblings Kayleigh and Tommy Miller, and Lenny, suffered many severe psychological traumas that frequently caused him to black out. These traumas include being coerced to take part in child pornography by Kayleigh and Tommy's father, George Miller (Eric Stoltz), being nearly strangled to death by his institutionalized father, Jason Treborn (Callum Keith Rennie), who is then killed in front of him by guards; accidentally killing a mother and her infant daughter while playing with dynamite with his friends; and seeing his dog being burned alive by Tommy.
Private investigator Tom Welles (Nicolas Cage) is contacted by Daniel Longdale (Anthony Heald), attorney for wealthy widow Mrs. Christian (Myra Carter), whose husband has recently died. While clearing out her late husband's safe, she and Longdale found an 8mm film which appears to depict a real murder of a girl, but Mrs. Christian wants to know for certain.
Financial TV personality Lee Gates, who offers up stock advice on his hit show "Money Monster," is held hostage by a viewer, Kyle Budwell, who lost all of his money following a bad tip from Lee during his show.
In AD 859, as the Tang Dynasty declines, a number of rebel groups are established, the largest of which is the House of Flying Daggers, based in Fengtian. Its members steal from the rich and give to the poor, gaining the support of the locals. Two police officers, Leo (Andy Lau) and Jin (Takeshi Kaneshiro), are ordered to kill the leader of the group within ten days.
In the 1960s, a young woman nicknamed Babydoll (Emily Browning) is institutionalized by her abusive widowed stepfather (Gerard Plunkett) at the Lennox House for the Mentally Insane after she is blamed for the death of her younger sister. The stepfather bribes Blue Jones (Oscar Isaac), an asylum orderly, into forging the signature of the asylum's psychiatrist, Dr. Vera Gorski (Carla Gugino), to have Babydoll lobotomized so she cannot inform the authorities of the true circumstances leading to her sister's death. During her admission to the institution, Babydoll takes note of four items that she would need to attempt an escape.
College students Paxton (Jay Hernandez) and Josh (Derek Richardson) are traveling across Europe with their Icelandic friend Óli (Eyþór Guðjónsson). In Amsterdam, the three meet a man named Alexei (Lubomir Bukovy), who convinces them to visit a hostel in Slovakia filled with beautiful women. The three board a train to Slovakia, where they encounter a strange Dutch businessman (Jan Vlasák). When they arrive at the hostel, they are greeted by Natalya (Barbara Nedeljáková) and Svetlana (Jana Kaderabkova), who invite them to the spa, and later to the disco. That night, Paxton and Josh sleep with Natalya and Svetlana, while Óli sleeps with the desk girl, Vala (Jana Havlickova). The next morning, they are surprised to see that Óli hasn't returned, and they are unable to contact him. They are later approached by a Japanese girl named Kana (Jennifer Lim), who shows them a photo of Óli and her friend Yuki (Keiko Seiko), who has strangely disappeared as well.
A career bank robber, Jack Foley (George Clooney), and a U.S. Marshal, Karen Sisco (Jennifer Lopez), are forced to share a car trunk during Foley's escape from a Florida prison. After he completes his getaway, Foley is chased by Sisco while he and his friends—right-hand man Buddy (Ving Rhames) and unreliable associate Glenn (Steve Zahn)—work their way north to Bloomfield Hills, a wealthy northern suburb of Detroit. There they plan to pay a visit to shady businessman Ripley (Albert Brooks), who foolishly bragged to them in prison years before about a cache of uncut diamonds hidden in his home.
The plot involves an obsession with the 23 enigma, which is the idea that all incidents and events are directly connected to the number 23, or to some number connected to 23.