The story follows a young boy named Gon Freecss, who was told all his life that both his parents were dead. But when he learns from Kite, an apprentice of his father Ging Freecss, that he is still alive and has since become an accomplished Hunter, Gon leaves his home on Whale Island (くじら島, Kujira Tō) to take the Hunter Examination (ハンター試験, Hantā Shiken) in order to become a Hunter like him. During the exam, Gon meets and soon befriends three of the other applicants: Kurapika, the last remaining member of the Kurta clan who wishes to become a Hunter in order to avenge his clan and recover their scarlet-glowing eyes that were plucked from their corpses by a band of thieves known as the Phantom Troupe; Leorio, a prospective physician who, in order to pay for medical school, desires the financial benefits that Hunters receive; and Killua Zoldyck, another twelve-year-old boy who has left his former life as a member of the world's most notorious assassin family. Among many other examinees, Gon continuously encounters Hisoka, a mysterious and deadly transmuter who takes an interest in him. After passing by many trials together, Gon and his friends end up passing the exam except for Killua, who fails after killing another applicant due to being controlled by his brother, Illumi, and runs away to his family's estate in shame.
After Gon and the others convince Killua to rejoin their side, Leorio and Kurapika depart temporarily for their own personal reasons, while Gon and Killua set for the Heavens Arena (天空闘技場, Tenkū Tōgijō), a skyscraper where thousands of martial artists compete daily in fighting tournaments, seeking to improve themselves and gain monetary rewards. There they meet a kung fu master named Wing who trains them in utilizing Nen, a Qi-life like energy used by its practicers to manifest parapsychological abilities, and is also considered to be the final requirement to pass the Hunter Exam. Sometime later, Gon and his friends reunite again in Yorknew City (ヨークシンシティ, Yōkushin Shiti) where they have a clash with the Phantom Troupe. During the occasion, two from the band of thieves are killed by Kurapika and he is forced to give up the chance of hunting down the rest in order to rescue Gon and Killua, who were captured by them, but not without succeeding in sealing the powers of their leader Chrollo Lucilfer.
A few days later, Gon and Killua achieve their objective and begin playing Greed Island, an extremely rare and expensive video game with Nen-like properties following some clues about Ging's whereabouts. While exploring the game, it is revealed that its scenario is actually set somewhere in the real world, created with Nen by a team led by none other than Ging himself. Outclassed by the difficulty of the challenges in the game at first, they are soon joined and trained by Biscuit Krueger, an experienced teacher of Nen and kung fu master. With the help of Biscuit, Gon and Killua train their Nen and learn to shape their abilities to their traits. During their stay on Greed Island, Killua takes a short break to apply for the Hunter Examination again, this time passes with success. The trio then complete the game together against all odds and Gon obtains the right to choose the artifacts from the game necessary to reunite with his father.
Gon decides to have Killua accompany him to meet his father using the artifacts, but they send them to meet Kite instead. The duo then decide to help with Kite's research, and upon discovering a giant insect limb the group discovers that it came from a man-sized Chimera Ant queen, an insect that devours other creatures and then gives birth to progeny that inherit the characteristics of the different species it has eaten. The queen washes up onto an island nation called the Neo-Green Life (N.G.L.) Autonomous Region, where she quickly develops a taste for humans and builds a colony powerful enough to overcome the population, especially after her offspring learn the power of Nen after consuming some Hunters. Upon facing the Royal Guard of the Chimera Ants, Kite sacrifices himself to allow Gon and Killua to flee and alert the Hunter Association. After weeks of preparation, the Association sends a team of some of their most powerful Hunters, including Netero, the president of the Association himself to defeat the Ants and their king Meruem, whose subjects secretly overthrew the government of the nearby Republic of East Gorteau (東ゴルトー共和国) as part of their plan of subduing all of mankind. Despite losing to Meruem in combat, Netero ends up killing him with a bomb implanted in his body that poisons him to death soon after. In the occasion, Gon has a showdown with Neferpitou, the Ant who killed Kite and despite having exacted his revenge is hospitalized and in critical condition.