Edo is a city that was home to the vigor and ambition of samurai across the country. However, following feudal Japan's surrender to powerful aliens known as the Amanto, those aspirations now seem unachievable. With the once-influential shogunate rebuilt as a puppet government, a new law is passed that promptly prohibits all swords in public. Enter Gintoki Sakata, an eccentric silver-haired man who always carries around a wooden sword and maintains his stature as a samurai despite the ban. As the founder of Yorozuya, a small business for odd jobs, Gintoki often embarks on endeavors to help other people—though usually in rather strange and unforeseen ways. Assisted by Shinpachi Shimura, a boy with glasses supposedly learning the way of the samurai; Kagura, a tomboyish girl with superhuman strength and an endless appetite; and Sadaharu, their giant pet dog who loves biting on people's heads, the Yorozuya encounter anything from alien royalty to scuffles with local gangs in the ever-changing world of Edo.

Staz Charlie Blood is a powerful vampire who rules the Eastern district of Demon World. According to rumors, he is a bloodthirsty and merciless monster, but in reality, Staz is just an otaku obsessed with Japanese culture and completely uninterested in human blood. Leaving the management of his territory to his underlings, Staz spends his days lazing around, indulging in anime, manga, and games. When Fuyumi Yanagi, a Japanese girl, accidentally wanders through a portal leading into the demon world, Staz is overjoyed. But just as he is starting to feel an unusual attraction to her, his territory is attacked, resulting in Fuyumi's untimely death. She turns into a wandering ghost and the crestfallen Staz vows to resurrect her as this would mean being able to travel to the human world, something he has always dreamed of. Blood Lad follows Staz and Fuyumi, soon joined by the spatial magician Bell and the half-werewolf Wolf, as they travel to find a magic that can bring humans back to life.

In his father's absence, teenager Ippo Makunouchi works hard to help his mother run her fishing boat rental business. Ippo's timid nature, his lack of sleep, and the sea smell make him an easy target for relentless bullies who leave him bruised and beaten on a daily basis. Mamoru Takamura, an up-and-coming boxer, rescues Ippo from a violent after-school incident and takes him back to the Kamogawa Boxing Gym for recovery. Takamura and his fellow boxers, Masaru Aoki and Tatsuya Kimura, are stunned by Ippo's powerful punches—a result of strong muscles developed through years serving his physically taxing family business. Following brief training under Takamura, Ippo impresses the other boxers in a practice match against prodigy Ichirou Miyata. He gains a rival in Miyata and a coach in Genji Kamogawa, the gym owner and a former boxer himself. As Ippo takes the first steps in his official boxing career, he faces off against a series of challenging opponents, each more powerful than the last. Victory, loss, and a cycle of dedicated training await Ippo on his journey to achieve greatness. With his tough body and unstoppable fighting spirit, the kind young man seeks to take on the world.

To be quiet and do as you're told, that's the cowardly choice. These are the words of Junk Dog, an underground fighter of Megalo Box, an evolution of boxing that utilizes mechanical limbs known as Gear to enhance the speed and power of its users. Despite the young man's brimming potential as a boxer, the illegal nature of his participation forces him to make a living off of throwing matches as dictated by his boss Gansaku Nanbu. However, this all changes when the Megalo Box champion Yuuri enters his shabby ring under the guise of just another challenger. Taken out in a single round, Junk Dog is left with a challenge: If you're serious about fighting me again, then fight your way up to me and my ring. Filled with overwhelming excitement and backed by the criminal syndicate responsible for his thrown matches, Junk Dog enters Megalonia: a world-spanning tournament that will decide the strongest Megalo Boxer of them all. Having no name of his own, he takes on the moniker of Joe as he begins his climb from the very bottom of the ranked list of fighters. With only three months left to qualify, Joe must face off against opponents the likes of which he has never fought in order to meet the challenge of his rival.