Tsuna goes through many predicaments in his progress of becoming the Vongola boss including fighting against escaped Mafia convicts posing as Kokuyo Junior High students. Later, The Varia, Vongola assassin squad, claim the right for their boss, Xanxus to be the true Vongola boss, and start a competition to decide it. To defeat the Varia, Reborn recruits most of Tsuna's schoolmates to become the Vongola guardians: Hayato Gokudera, a dynamite expert who wishes to be his right-hand man, Takeshi Yamamoto, a baseball player who thinks the Mafia is a game, Ryohei Sasagawa, the energetic captain of the school boxing club, and Kyoya Hibari, the deadly head prefect. Lambo, a weak infant assassin who came to kill Reborn, and Chrome Dokuro, a girl who has a mental and physical link with the criminal Mukuro Rokudo, joins them as well. Later, after defeating the Varia, Tsuna and his friends are transported to the future where they must face the Millefiore Family, who are annihilating the Vongola. They also find that all the Arcobaleno are dead except for Reborn from the past. As Tsuna and the Vongola Guardians from his time fight the Millefiore they learn that Shoichi Irie, a comrade of Tsuna's future self, was the one who sent them to the future as the future Tsuna said they were the only ones who can defeat the Millefiore leader Byakuran. It is later revealed that Byakuran has gained knowledge from parallel worlds and that he wants to obtain all the Mafia rings in order to obtain a power similar to omniscience.
After defeating Byakuran, Tsuna and company return to the present where they learn that Tsuna is to undergo the inheritance ceremony to officially become the 10th boss of the Vongola Family. However, the ceremony is attacked by the Shimon Family, who have sworn revenge on Vongola Primo for supposedly betraying the first Shimon boss. Using the power of the Shimon rings, they have destroyed the Vongola Rings, left Yamamoto hospitalised and kidnapped Chrome. However, a man named Talbot reconstructs the Vongola Rings into the Vongola Gear, and Tsuna and the remaining guardians go to Shimon's hideout where they must face the Shimon family in battles with their pride on the line. In addition, whoever loses in either side will be taken away by Vindice into prison forever. Each battle won or lost, they will receive a key. While the various battles take place it is revealed that Daemon Spade, a member of the first generation Vongola boss's family, is the one who kidnapped Chrome and has a dark agenda in the battle between these rival families.