After a horrific alchemy experiment goes wrong in the Elric household, brothers Edward and Alphonse are left in a catastrophic new reality. Ignoring the alchemical principle banning human transmutation, the boys attempted to bring their recently deceased mother back to life. Instead, they suffered brutal personal loss: Alphonse's body disintegrated while Edward lost a leg and then sacrificed an arm to keep Alphonse's soul in the physical realm by binding it to a hulking suit of armor. The brothers are rescued by their neighbor Pinako Rockbell and her granddaughter Winry. Known as a bio-mechanical engineering prodigy, Winry creates prosthetic limbs for Edward by utilizing automail, a tough, versatile metal used in robots and combat armor. After years of training, the Elric brothers set off on a quest to restore their bodies by locating the Philosopher's Stone—a powerful gem that allows an alchemist to defy the traditional laws of Equivalent Exchange. As Edward becomes an infamous alchemist and gains the nickname Fullmetal, the boys' journey embroils them in a growing conspiracy that threatens the fate of the world.

Hunters devote themselves to accomplishing hazardous tasks, all from traversing the world's uncharted territories to locating rare items and monsters. Before becoming a Hunter, one must pass the Hunter Examination—a high-risk selection process in which most applicants end up handicapped or worse, deceased. Ambitious participants who challenge the notorious exam carry their own reason. What drives 12-year-old Gon Freecss is finding Ging, his father and a Hunter himself. Believing that he will meet his father by becoming a Hunter, Gon takes the first step to walk the same path. During the Hunter Examination, Gon befriends the medical student Leorio Paladiknight, the vindictive Kurapika, and ex-assassin Killua Zoldyck. While their motives vastly differ from each other, they band together for a common goal and begin to venture into a perilous world.

The year is 1868; English nobleman George Joestar and his son Jonathan become indebted to Dario Brando after being rescued from a carriage incident. What the Joestars don't realize, however, is that Dario had no intention of helping them; he believed they were dead and was trying to ransack their belongings. After Dario's death 12 years later, George—hoping to repay his debt—adopts his son, Dio. While he publicly fawns over his new father, Dio secretly plans to steal the Joestar fortune. His first step is to create a divide between George and Jonathan. By constantly outdoing his foster brother, Dio firmly makes his place in the Joestar family. But when Dio pushes Jonathan too far, Jonathan defeats him in a brawl. Years later, the two appear to be close friends to the outside world. But trouble brews again when George falls ill, as Jonathan suspects that Dio is somehow behind the incident—and it appears he has more tricks up his sleeve.

Edward Elric, a young, brilliant alchemist, has lost much in his twelve-year life: when he and his brother Alphonse try to resurrect their dead mother through the forbidden act of human transmutation, Edward loses his brother as well as two of his limbs. With his supreme alchemy skills, Edward binds Alphonse's soul to a large suit of armor. A year later, Edward, now promoted to the fullmetal alchemist of the state, embarks on a journey with his younger brother to obtain the Philosopher's Stone. The fabled mythical object is rumored to be capable of amplifying an alchemist's abilities by leaps and bounds, thus allowing them to override the fundamental law of alchemy: to gain something, an alchemist must sacrifice something of equal value. Edward hopes to draw into the military's resources to find the fabled stone and restore his and Alphonse's bodies to normal. However, the Elric brothers soon discover that there is more to the legendary stone than meets the eye, as they are led to the epicenter of a far darker battle than they could have ever imagined.