Naruto Uzumaki is a young boy who has the Nine-Tailed Demon Fox sealed within him. Twelve years before the start of the series, the Nine-Tailed Demon Fox attacked the ninja village Konohagakure, slaughtering many people. In response, the leader of Konohagakure and its ninja military – the Fourth Hokage – sacrificed his life to seal the demon inside Naruto when he was a newborn. Konohagakure, however, regarded Naruto as if he were the demon fox itself and mistreated him throughout most of his childhood. A decree made by the Third Hokage, who replaced the Fourth Hokage after his death, forbade anyone mention the attack of the demon fox to anyone else. This included Naruto, who was not aware of the demon inside of him.

Years later, Naruto is tricked by the renegade ninja Mizuki into stealing a forbidden scroll, but he is stopped by his teacher, Iruka Umino. When Iruka almost dies while protecting Naruto from Mizuki, Naruto uses a supernatural ability Jutsu he learned from the scroll that creates multiple clones of himself, Shadow Clone Technique, to defeat Mizuki. This encounter leads Naruto to realize that he is the container of the demon fox.

The main story follows Naruto and his friends' personal growth. Naruto befriends two comrades, Sasuke Uchiha and Sakura Haruno, who are assigned with him to form a three-person team named Team 7 under an experienced sensei named Kakashi Hatake. Like all the ninja teams from every village, Team 7 is charged with completing missions requested by villagers, such as doing chores or being bodyguards. During the course of their missions, Naruto befriends other characters that he meets throughout the series. Team 7 learns new abilities, get to know each other, and experience a coming-of-age journey as Naruto dreams of becoming the Hokage of Konohagakure.

After several missions, Kakashi allows Team 7 to participate into a ninja exam in which they can improve their ranks, and thus, take part in more difficult missions. During the exams, Orochimaru, a criminal at the top of Konohagakure's most wanted list, attacks Konoha and kills the Third Hokage in an act of revenge. This forces one of the three legendary ninja, Jiraiya to search for his former teammate Tsunade, who has been nominated to become the Fifth Hokage. During the search, it is revealed that Orochimaru desires to acquire Sasuke Uchiha due to his powerful genetic heritage. Believing Orochimaru will be able to give him the strength needed to kill his brother Itachi, who destroyed his clan, Sasuke goes to him in search of power. Tsunade sends a group of ninja including Naruto to make Sasuke return to Konoha, but Naruto is unable to defeat him and bring him back to the village. Naruto does not give up on Sasuke, however, and he leaves Konoha to train for two-and-a-half years under Jiraiya's tutelage in order to prepare himself for the next time he encounters Sasuke.

After the training period, a mysterious organization called Akatsuki attempts to capture the nine powerful tailed beasts including the Nine-Tailed Demon Fox sealed inside of Naruto. Several ninjas from Konohagakure, including Team 7, fight against the Akatsuki members and search for their teammate Sasuke. Although they manage to save Gaara the host of the One-Tailed beast, Akatsuki is successful in capturing seven of the creatures. In the meantime, Sasuke betrays Orochimaru and faces Itachi to take revenge. Although Itachi dies in battle, Sasuke is later told by the Akatsuki founder Madara Uchiha that Itachi was ordered by Konohagakure's leadership to destroy his clan. Saddened with this revelation, Sasuke joins forces with Akatsuki to destroy Konohagakure. Meanwhile, as several Akatsuki members are defeated by the Konohagakure ninja, their leader, Pain, invades the village to capture Naruto. However, Naruto defeats Pain's multiple bodies and convinces the real one to leave Akatsuki..