Um estranho bebê, Reborn, alegando ser um assassino da máfia se aproxima de Tsunayoshi "Tsuna" Sawada. Para desânimo de Tsuna, ele acaba de ser escolhido para se tornar o próximo chefe vongola.

Desde a chegada de Reborn, Tsuna começa a conhecer pessoas novas e estranhas. Uma dessas pessoas é Hayato Gokudera, um membro da máfia que quer matar Tsuna para se tornar o chefe vongola. Enquanto isso, Tsuna é forçado a ajudar a equipe de vôlei, incluindo seu amigo Takeshi Yamamoto, devido à sua demonstração de força no episódio anterior.

Tsuna agora tem dois subordinados: Gokudera e Yamamoto. Mas as coisas não vão bem e começam a aparecer várias pessoas atrás de Tsuna. Dentre eles, temos Lambo, da família Bovino e Bianchi, a irmã de Gokudera e antiga parceira de Reborn!

Tsuna descobre a garota Haru, que é fascinada pelo Reborn. Em meio a isso, Tsuna recebe outra nota ruim na escola e precisa pensar, junto com seus amigos, em uma forma de não repetir de ano.

Justamente quando Tsuna está se adaptando à sua nova vida, o líder delinquente de sua escola, Kyoya Hibari, agora tem como alvo Tsuna. Felizmente para Tsuna, Hibari está mais interessado em lutar contra Reborn.

A casa de Tsuna está bem cheia com seus novos amigos. Isso faz com que Tsuna não consiga tomar café da manhã. Ao ir para a escola com fome, encontra uma barraquinha de comida chinesa. E acaba salvo por um garoto chinês misterioso.

Tsuna combinou de se encontrar cedo com Kyoko, mas acabou esquecendo. Agora ele precisa que Reborn o ajude a chegar na hora! No entanto, ele acaba levando junto com ele Ryohei, irmão de Kyoko e capitão do clube de boxe. Agora Ryohei quer Tsuna no clube!

Tsuna chega em casa e nota um número grande de engravatados. Quando chega em casa, encontra Dino, o chefe da família Cavallone e o último discípulo de Reborn antes de Tsuna. Dino começou como Tsuna, sem querer se tornar chefe e chegou ao sucesso. Tsuna também conseguirá fazer o mesmo?

Tsuna é afligido pela misteriosa Doença da Caveira e vai morrer se não conseguir a cura até o pôr do sol. Reborn está pronto para ajudá-lo e chama do Dr. Shamal da Itália, um mulherengo inveterado. No entanto, ele deixa bem claro que só atende mulheres...

Tsuna esquece o almoço ao sair de casa e sua mãe encarrega Lambo de ir entregar. Mas no caminho, o mesmo pacote do almoço é trocado por um pacote de nitroglicerina de I-Pin, colocando em risco toda a escola!

Reborn convence Tsuna a confessar seus sentimentos para Kyoko. No entanto ele não consegue fazer isso em um primeiro momento. Ele encontra Haru e ambos saem juntos, mas acabam encontrando Kyoko e as meninas resolvem fazer um programa juntos. Nisso, elas acabam comendo um gyoza misterioso e ficam à beira da morte.

Reborn fortalece as habilidades de Gokudera e Yamamoto através do "programa de fortalecimento", que parece ser mais do que um curso de exercícios. Quando Gokudera descobre que Reborn e Tsuna parecem estar prestando mais atenção em Yamamoto, ele se sente excluído.

Começa um novo ano e Reborn convida a família Vongola e a família Cavallone para participarem de uma competição de ano novo. No entanto, quem perder a competição ficará devendo 100 milhões de ienes para a outra família. E o jogo não começa bem para Tsuna...

Tsuna goes to the zoo with Kyoko, and is glad to finally able to be alone with her. Tsuna's ideal "date" does not go as planned, however, as he runs into his friends in the zoo, who are causing all sorts of trouble.

All of Tsuna's friends show up at school during winter to help him babysit I-pin and Lambo. Although, in a turn of events, everyone besides Tsuna seems to just want to have a snowball fight, so Reborn turns it into another one of his staged competitions.

When Reborn drops Tsuna and his friends off on an isolated mountain, he and others become lost in the wilderness of the mountain.

Tsuna is recovering from his wounds from the previous episode and discovers that recovering in peace and quiet isn't possible with not only his friends visiting, but the fact that Hibari is in the same hospital.

It's Valentine's Day Kyoko and Haru are at Tsuna's house to make some chocolate, only to his horror to find that they are being helped by Bianchi. Tsuna and his friends have to find away to get Bianchi away from them before she ends up poisoning the chocolate.

A small kid named Futa bumps into Tsuna. What Tsuna is not aware of is that Futa is a Mafia informant, whose "rankings" are 100% accurate, and this makes him a widely sought-after target, forcing Tsuna and the others to protect him.

One by one, students at Namimori High are being targeted by an unknown gang. It seems that some of those targets are some of Tsuna's friends, and he has to stop the unknown gang before they attack his friends.

After a battle between Gokudera and Chikusa, one of the gang members; Tsuna, Yamamoto, Gokudera, Bianchi, and Reborn set off to capture and defeat the mysterious gang from Kokuyo, only for Yamamoto to run into trouble right off the bat.

After a quick battle between Bianchi and M.M., Haru and Kyoko have been targeted by the serial killer twins Jiji and Didi under Birds' order. Threatening to kill off the girls, Birds plays with Tsuna and his friends, commanding them to beat Tsuna up.

With Tsuna running after Futa, the others are left to deal with the one claiming to be Mukuro himself. He proves to be too much for them in the state they are in, so all hope lies with Tsuna coming back in time. However, even if he does, there is only one Dying Will Bullet left.

With the reveal that their foe wasn't the real Mukuro, everyone breaks into the Kokuyo Middle School building to face the true mastermind. With no Dying Will, Gokudera having to fend off both Chikusa and Ken, and everyone else unconscious, all hope looks lost, but one of Mukuro's captives my prove to be the ace in the hole.

Even after his apparent death, Mukuro still isn't finished as he possesses the bodies of everyone his hit with his trident. There seems to be no way for Tsuna to win with everyone under Mukuro's control and no Dying Will, when Reborn's pet Leon gives off a strange glow.

With the new Rebuke Bullet, Tsuna has reached a new level of power, but it still may not be possible to defeat Mukuro, who still has not revealed his strongest form.

After the defeat of Mukuro, life goes on normally and Tsuna and his friends all move up a grade at school. However, none of them are in the same class, so Reborn offers them a challenge to catch him, with the prize being a change of the roster. Later, they celebrate at a sushi restaurant owned by Yamamoto's father only to find they do not have enough money to pay for their food and have to work off their debt.

Kyoko's friend Hana is infatuated with Future Lambo and blackmails Tsuna into letting her meet him by threatening to tell Kyoko that Haru is his girlfriend. When Lambo uses the Ten-Year Bazooka, however, something malfunctions and creates a teen Lambo with young Lambo's mind, and to make matters worse, this Lambo escapes from the house.

Reborn invites Tsuna and his mom to a vacation resort, but they first have to ride on a cruise ship to get there. Once on the ship, Tsuna spots some of his friends, who all boarded without tickets, and he now has to keep them from being caught, but first, he has to catch them.

At Mafia Island, Tsuna fails to prove his identity as the Vongola Family's 10th boss, and is transported to the back of the island where he is given a new chance to prove himself. There, he meets another Arcobaleno, Colonello. Colonello and Reborn put Tsuna through tough training. Meanwhile, another Arcobaleno invades the island with an army.

Tsuna has to swim 15m in school, but being unable to swim, he is trained by Yamamoto, Gokudera and Haru in the public pool. Everyone has his own method, and they decide to compete to see who can get Tsuna to swim the furthest. Reborn interferes this time with a Vongola dolphin that has a dangerous complexion.

To pay off the damage caused in the previous episode, Tsuna works as a lifeguard with Ryohei, only for them and the other boys to be challenged to a swimming race by older lifeguards. Later, Tsuna and his friends run a stand during a summer festival to continue to pay off their debt, only to have run ins with Hibari, and a group of thieves.