The story of Hamatora revolves around a 17-year-old teenager called 'Nice', who runs a private investigation agency called 'Hamatora' in Yokohama, Japan with his partners Hajime and later, Murasaki.

In the world there is the existence of Select humans called Minimum Holders (ミニマムホルダー, Minimamu Horudā) have been discovered to possess supernatural abilities known as 'Minor Miracles' or 'The Minimum'. These people are trained in the Facultas Academy to develop their potential, and are given highly advanced classes and training to do so. As a result, those who graduate from Falcultas are given extreme benefits and privileges that enable them to be highly successful in life, such as being entitled to any job or career they want with ease. The existence of minimums and minimum holders is kept extremely confidential and secretive from the general population of the world.

The events of 'Hamatora The Comic' takes place in the year 2013, with Nice having left Falcutas academy early in his first senior year. Due to Nice both being a genius and a prodigy, Murasaki, the second highest ranked graduate from Falcutase, is tasked with the mission of bringing Nice back to Falcultas by any means necessary. As Murasaki first meets Nice, his impressions of him leave Murasaki feeling insulted and angered that someone as easy going and immature like Nice could be superior to him. As Murasaki observes Nice on his jobs though, Murasaki finds himself assisting Nice and comes to see the potential Nice actually possesses as well as acknowledging his genius. He also dwells on Nice's views on Falcultase's workings and his opinion of how people with minimums are not slaves and are free to live their lives responsibly.

During the job where Sayuri Akatasuki (Akatsuki Sayuri) requests for Nice and to rescue her sister Shizuku, a minimum holder who can generate fire, from a criminal family. Nice and Murasaki finish their job but Murasaki is tasked to leave Nice and to take Shizuku back to Falcultas as part of the academy's dark dealing with the mafia family. As Murasaki takes Shizuku to Falcutase, Nice, Hajime and Sayuri are attacked by Falcutas and the Hamatora office is destroyed. As Murasaki hands over Shizuku, he struggles on the decision he made and ends up trying to rescue Shizuku from Falcutas. Nice, who managed to save himself, Hajime and Sayuri before defeating the Facultas agents, ends up saving Murasaki, but during the confrontation with Falcutas and the mafia family, Shizuku apparently dies. In the week that follows, It is then revealed that Shizuku survived and faked her death so that she and Sayuri and live a new life without fearing her minimum or Falcultas and the Mafia Family. Murasaki has since left Falcultas and has joined Nice as a Hamatora P.I. which is now located in Cafe Nowhere along with Birthday and Ratios 'Odd Jobs' Business and Honey and Threes Bodyguard business.

During the anime, Murasaki has joined Nice as a Hamatora P.I. now based in the Cafe Nowhere in Yokohama where they prefer to sit around all day with their friends and wait for clients. During their Jobs, Nice finds similarities in the working of several crimes he investigates and the existence of non-innate minimum holders; people who possess a minimum but where not born with it. Nice and Murasaki are warned by their friend, Art, a non minimum holder who still managed to graduate from Falcultas, about a minimum holder seriel killer who extracts the brains to create more minimum holders. The culprit is Moral, a former professor from the Facultas Academy who wishes to give everybody Minimums in order to achieve equality. For this, he has to kill several Minimum Holders and use their brains to create a substance he calls 'essence' that enables him to create 24 non-innate minimum holders for every minimum holder brain he possesses. While his overall purpose in this is to create equality, what Moral truly wants is to save Nice, as he believes that Nice is tortured by solitude as he is the number one student of falcultas, also calling him the accumulated wisdom of humanity, and therefore has no equals.

Moral kills Art and starts assuming his identity to dismiss the Hamatora from the case. With his assistant, Momoka, he implants several of his followers with Minimums and starts a riot in order to expose the existence of minimum holders and Momoka also leaks information exposing the existence of Facultas academy and minimum holder identities, causing disturbance in society as normal people treat minimum holders in a hostile manner while minimum holders fight back to ensure their right to exist. After discovering Moral took Art's face, Nice confronts him in person to get revenge for his best friend's death. The two face in a ship which Moral is using to perform a terrorist attacks on non-Minimum Holders. As Nice defeats Moral, the murderer is killed by Art, who seems to be alive, who then points his gun at Nice.

The events of Re: Hamatora will follow Hajime and Murasaki as they form Hamatora Mark Two following the apparent death of Nice.