Ryo Saeba works the streets of Tokyo as the City Hunter. He's a "sweeper" and with his sidekick Kaori Makimura, he keeps the city clean. People hire the City Hunter to solve their dangerous problems, which he does with a Colt Python. When Ryo's not working on a case, he's working on getting the ladies, and Kaori must keep him in check with her trusty 10 kg hammer.
Ryo's old friend Robert Harrison arrives in Tokyo for some sightseeing, but with an important job to take care of, Ryo decides to let Robert in on his mission: to protect Princess Angela of the Felidan Kingdom while she attends peace talks at a secret villa to settle a civil war. The two meet with the princess and General Marukido, whom with Ryo already has suspicions. This is confirmed when Ryo is able to take down some assassins and the plot is revealed: to blow up the villa where the peace talks are being held.
Ryo meets Shoko, a young girl who believes money is everything and is better than love. While Ryo tries to turn Shoko's attitude around, he has to contend with three men attempting to court her on behalf of a friendly Yakuza group.
Ryo notices that he is being watched by Kozue, a 12 year old girl confined to a wheelchair. When he pays her a visit, Kozue remarks that he is the second person to notice her, the first being a mysterious man with a beard. Kaori suspects that Ryo is using Kozue to get to her much older sister. But when the mysterious man attacks Kozue, Ryo decides to have Kozue and her sister live with him until he can figure out what is going on.
Ryo's client is a young girl with a unique telepathic ability to read minds. However, Ryo is smitten by the girl's nanny, a woman with martial arts skills. The young girl, Sara, is entranced by Ryo and his abilities, despite the fact that his mind is filled with "Mokkori" most of the time. It turns out that Sara is the only daughter of the head of a large family conglomerate and that many of her relatives are after her. Sara also runs into a disturbing fact: that Kaori is secretly in love with Ryo.
On her way to take on David Clive, the terrorist who is holding her lover hostage, Bloody Mary finds out that Kaori has snuck in the vehicle with a large cache of weapons. The duo proceed to bust into David Clive's hideout, with Ryo and Umibozu in hot pursuit. But when David Clive forces a gun into the head of Bloody Mary's lover, Ryo and Bloody Mary are forced to fight each other.
Kozue begins to enjoy life with Ryo and decides to try to set him up with her older sister. Meanwhile, Ryo finds out that Kozue was wounded by an unknown man who had killed another over a deal gone bad, and the bullet stuck against her spine is the cause of her paralysis. The arrival of Detectives Iwadate and Saeko also begins to complicate matters. With Kozue scheduled to undergo an operation which may allow her to walk again, Ryo realizes that Kozue may be in greater danger than initially thought.
Ryo suspects that Interpol Agent Nelson may in fact be in league with the revived Red Pegasus drug cartel. After a boat chase, the information of the drug smuggling route is revealed, the route ends at an orphanage that Hideyuki visited shortly before his death, and that a postcard addressed to him from the orphanage was meant to lead Kaori to that location.
Ryo runs into Kasumi Asoh, the "flying tush object" he met several years earlier. Kasumi is now 19 and is set to go into an arranged marriage in which she wants no part of. She thus masquerades Ryo as her lover, much to the disapproval of her grandmother, and Takeshi, Kasumi's arranged husband. Takeshi uses unscrupulous tricks against Ryo, by first hypnotizing him into believing that Takeshi's "mokkori" is bigger than Ryo's then when Ryo finds out about the hypnosis, hypnotizes Ryo in a state in which he can no longer experience "mokkori".
His mokkori "kidnapped", Ryo must try to defeat Takeshi in a showdown between thieves by stealing a magic mirror. But when Takeshi is able to obtain the mirror using another hypnotic trick, Ryo does not pursue. He mentions that there is a secret behind the mirror and that it was never meant to be stolen. Thus Takeshi has lost but Kasumi's grandmother discovers that Kasumi has fallen in love with Ryo. She then forbids Kasumi to return to the family estate and thus Kasumi boards with Umibozu and Miki at the Cat's Eye.
Ryo is hired to protect Princess Alma, an apparently bratty young but smart girl, as well as her servant, the beautiful Salina. When Ryo initially refuses to do the job, Princess Alma offers to give him his very own personal "harem" in their home nation. But Ryo is enchanted by Salina, but is unable to touch not only out of fear for losing the harem, but because Salina possesses a strange aura that prevents Ryo from touching her. Kaori discovers the truth about Alma and Salina, that they had switched identities in order to throw Ryo off. But when Kaori and the real servant plant an idea that Salina (who is really Alma) is really a man, the real Princess Alma gets upset and runs away, realizing that she has fallen in love with Ryo.
After Ryo, Saeko, and Umibozu are able to thwart an ambush set up by Sarah, her group, the Black Army, makes a ransom demand to the Japanese government with the threat of blowing up a nuclear bomb in the heart of Shinjuku. With the information on their hideout from Rumi, Ryo decides to take the Black army on. But when he realizes the truth of Sarah's identity, he finds that he is unable to shoot her.
An airliner is hijacked and all of the women are being held captive. After assisting in dealing with the hijackers, Ryo makes off with Misa Williams, unaware that she is the daughter of the leader of the opposition in the Pamela Republic. Saeko, hired to guard Misa by General Jimetil, ruler of the Pamela Republic, gives chase along with Kaori. After intercepting Ryo and Misa at a bathhouse where Ryo has taken care of two men trying to kidnap Misa, Saeko informs them that General Jimetil has been overthrown by the opposition.
Ryo has an unfortunate encounter with a schoolgirl as Kaori interviews a potential client asking the City Hunter to protect his grand-daughter, Kimiko. It turns out Kimiko is the same girl whom Ryo had met earlier and both of them do not get along well. It appears that there are many men after Kimiko for unknown reasons, and Kimiko devises a plan to masquerade Ryo as her fiance. Ryo decides to investigate further and finds out that Kimiko may well be related to a wealthy matriarch.
Sara is instantaneously jealous of Kaori's love for Ryo, but is able to come to terms with her feelings and cements a friendship with Kaori. Meanwhile, henchmen try to hire Umibozu to kill City Hunter but Umibozu instead gift wraps them for Ryo. They find out that Sara's Uncle was responsible for her father's death, and is trying to have Sara killed so he can inherit the family estate. Ryo decides to confront the Uncle directly.
Kaori makes plans to throw a party for the orphans at Kusunoki house but Ryo refuses to participate. When she finds out that Kusunoki house is to be closed down by the owner of the land, Mr Ookouchi, she requests Ryo's help only to be turned down. Believing that the proprietor, Mr Hitiyoshi, may have been cheated out of the ownership certificate for the house, Kaori takes matters into her own hands by breaking into Ookouchi's safe and stealing several documents including the land ownership certificate. Ookouchi's men react by ransacking Kusunoki house and kidnapping one of the kids as ransom for a certain document.
The Villa explodes, and while the Princess and the peace talk participants are able to escape, Robert appears to have been caught in the blast. Ryo tracks down General Marukido and is prepared to kill him when a twist is revealed: Robert is actually alive. When Robert reveals his true colours and attempts to assassinate the princess, Ryo must face his former partner in a showdown.
A girl named Maiko refuses to have a life-saving operation unless she sees the hero of her dreams, an unknown man by the name of Tetsu. In fact, Tetsu is trying to join a Yakuza group, and Ryo must save him from a potentially dangerous fate.
Kaori tries to convince Ryo to find Salina (who is really Princess Alma). But when the real Salina is kidnapped by the perpetrators, Ryo, still unaware of the identity switch, must save her from the trap that the perpetrators have planned, all this while protecting the real Princess Alma.
Sayuri takes Kaori shopping and gives her a complete makeover. As they are proceeding back to the apartment, they are kidnapped by unknown strangers. Ryo is able to determine that the men responsible are members of the Unryu-Kai, of whom Ryo once dealt with. Once the women are freed, only one question remains, will Sayuri tell Kaori the truth about her existence?
Kaori discovers Ryo in bed with another woman and angrily leaves him as a result. Ryo, with no recollection of the events the night before, decides to strike it up with this woman. What he does not realize that the woman, Rumi, is the daughter of a powerful Japanese politician. In his anger, the politician hires Umibozu to take out the City Hunter and retrieve Rumi. But Ryo realizes that some men are also after Rumi, led by a mysterious woman named Sarah.
Ryo and Kaori attempt to protect a female lawyer marked for death by a corrupt developer, after an electronic databook is accidentally left in her possession.
General Jimetil, formerly of the Pamela Republic, flies to Tokyo as an exile. At the same time, his personal guard tries to make a strike against Ryo in order to acquire Misa as a stake against her father. While they are unsuccessful in trying to kidnap Misa, they are able to grab Saeko. Ryo must attempt to try to save Saeko without sacrificing Misa's safety.
When a car bomb gravely injures a young girl, Saeko is furious and vows to bring down the people responsible. In order to do so, she must secretly request Ryo's help to bring down a robbery gang. The trail leads to a suave womanizer and Kaori is kidnapped when she tries to go after robbers who rob her of her remaining life savings.