In Philadelphia, Detective Bowden is still grieving for his wife and son, killed in a hit-and-run five years ago. When someone jumps from a skyscraper onto a truck, Bowden is sent to investigate. Meanwhile, five strangers are trapped in an elevator in the building where the jumper committed suicide. The communication radio in the elevator is broken but the guards, Lustig and Ramirez, observe the individuals via CCTV as events unfold. Tensions run high among those trapped, so Lustig calls the police and Detective Bowden assumes the case. Without being able to contact the individuals, he tries to work out who they are, but he can only account for four of them. Time is running out for the occupants of the elevator, as Bowden realizes he has to get them out quickly.

Twelve-year-old Ann Uekusa and her mother move to the small town of Shimane, where Ann's grandparents live and everyone seems to be familiar with everyone else. Ann soon becomes friends with Daigo, a young boy who lives in Shimane, as well as Fuji and Shika, Fuji's younger sister and her best friend in Shimane. When Ann's mother, Miwako, commits suicide, Daigo helps Ann cope with the sudden change in her life. They fall in love, but Ann's life can only become more complicated when her estranged father suddenly arrives from Tokyo. After greatly contemplating going to Tokyo to live with her father after he asks her, she decides to stay. Ann tells Daigo about her decision but makes her go anyway. Ann and Fuji both live in Tokyo but hardly ever talk because Fuji goes to an elite high school, K High. Ann met back up with her friends she had before moving to Shimane and they continue their friendships. In Tokyo, she ends up becoming closer to Fuji, which causes conflict between her and Daigo.In Shimane, Shika learns the truth about her parentage and in her confusion, she begins to fall in love with Daigo. When Ann returns to Shimane, Shika upsets Ann's fragile emotional state so that Ann and Daigo will break up. In the end, Ann breaks up with Daigo for fear that her own sadness will weigh him down. Ann returns to Tokyo and starts a relationship with Fuji; however, because she does not love him, the relationship does not last. Daigo refuses Shika and rumors begin to circulate that he is interested in his middle school classmate Ayumu, who has been helping him studying to get into university and become a teacher.Nearing graduation, Ann learns that her father and his friend Kaede Kuroki have been dating and she is pregnant with Ann's half-sister. Ann's father and Kaede marry after being encouraged by Ann and Ann's grandmother. Fuji, now aware that Shika was the child of his mother's affair rather than himself, supports her decision to studying abroad in Vancouver so that she can learn not to rely on others. Daigo and Ann make it to the post-secondary institutions of their choice while Fuji must repeat his senior year after running away from home.After attending her middle school reunion, Ann spends some time with Daigo, where he tells her to find her own happiness. Six years later, Ann meets a young businessman named Keiichiro Sakura and they become engaged shortly after. After Ann learns that he only uses people for his own gain, she confronts him about his insensitivity, but he is disappointed in her and breaks off the engagement. Almost a week afterward, she takes a train to Okayama, where Daigo teaches elementary school. Ann's grandmother, meanwhile, believes Ann will suffer the same fate as her mother. After a failed suicide attempt on the beach, Ann is taken to the hospital and later meets Daigo, who asks her to marry him. She says yes and at the very end the two are shown to be happily married with an infant son named Ryo. Meanwhile, Fuji decides to marry his cousin Mariko (against his family's wishes) and Shiika decides to work for her uncle in America.

When Bobby Saint and Mickey Duka meet with European arms dealer Otto Krieg at the Tampa, Florida seaport, the FBI intervenes and Saint is killed while Duka is jailed. "Krieg", supposedly killed in the shootout, is actually undercover FBI agent and former U.S. Army Delta Force operator Frank Castle. Shortly thereafter, he retires from the FBI and attends a family reunion at his father's oceanside home in Aguadilla Bay, Puerto Rico. Tampa crime boss Howard Saint is enraged by the death of his son, and with right-hand man Quentin Glass bribes the FBI for confidential information about "Krieg". Saint orders Castle murdered, and Saint's wife, Livia, demands Castle's entire family be killed as well to "settle the score". At the reunion, gunmen including Glass and John Saint, Bobby's identical twin, kill most of the extended family. Castle and his father kill several of the attackers before Castle's father is killed. Castle's wife and son try to escape in a Jeep, but Saint runs over them with a truck, killing them. Castle, shot in the chest and blown off a pier in an explosion set by Glass, survives and is nursed back to health by a local fisherman, Candelaria. Once recovered, Castle goes to Tampa and takes refuge in an old tenement where three young outcasts — Dave, Bumpo and Joan — live. Castle abducts Duka, who fearfully gives up information about the Saints — whom he, too, hates, and so willingly becomes Castle's mole. Castle starts exacting revenge on the police and FBI agents who have been bribed to close the investigation of his family's murder. In the process, he sabotages Saint's money-laundering business and severs Saint's partnership with Cuban mobsters the Toro Brothers, and starts tailing Livia and Glass, whom he learns is a closeted homosexual. Saint, realizing Castle is alive, sends two assassins to kill him. Castle kills the first, guitar player Harry Heck, by shooting a ballistic knife into Heck's throat. The second is "the Russian", a behemoth who beats Castle in a brutal fight but is defeated when Castle throws boiling oil in his face, blinding him long enough for Castle to throw him down a staircase, breaking his neck. Moments later, Saint's men arrive, led by Glass and John Saint. Dave, Joan and Bumpo hide Frank and refuse to tell Glass where he is, despite Glass sadistically pulling out Dave's multiple facial piercings with a pair of pliers. They leave a man behind to kill Castle upon his return, but Castle kills him once Glass and the others are gone. With assistance from Mickey, Castle manipulates Saint into believing Glass and Livia are having an affair. Saint, unaware Glass is gay, and believing Livia to be capable of cheating on him, kills them both personally, neither of them knowing why. Castle attacks Saint's headquarters, the downtown Tampa nightclub Saints and Sinners, killing many of Saint's henchmen. He kills John Saint by having the crime boss' son hold an eight-pound, trip-wire activated grenade until his arm wearies and the grenade explodes, killing him. Castle wounds Howard Saint with a pistol when Saint attempts to shoot him in the parking lot of the nightclub. Castle then ties Saint to a slow-moving car, but not before revealing that Glass and Livia were not having an affair. Several hidden bombs go off, and the destruction and wreckage culminate in the shape of the Punisher's iconic skull. Later that night, Castle returns to his apartment and prepares to commit suicide, but after a brief vision of his wife, decides to continue his vigilante mission against others who in his mind deserve punishment. Before departing on his next mission, he leaves most of Saint's money for Bumpo, Joan and Dave. On the Sunshine Skyway Bridge, he vows, "Those who do evil to others — the killers, the rapists, psychos, sadists — will come to know me well. Frank Castle is dead. Call me the Punisher."