Not much is known about Squalo's past. He was a child prodigy in most sword arts, including fencing. He and Dino attended the same school, a school for children of the mafia, when they were younger. Around this time, he met Xanxus at a Mafia event and was impressed by the latter's rage.
From a young age, he was determined to get stronger and make others submit to him. To achieve this goal, he traveled extensively and defeated various swordsmen. At the age of fourteen, Squalo fought and defeated the first Sword Emperor and first Varia boss, Tyr. In doing so, he became the second Sword Emperor and was expected to become the next Varia boss, but instead handed the position to Xanxus. Soon afterwards, along with the rest of the present Varia members, Squalo helped Xanxus launch a coup d'etat against Vongola Ninth. The attack was unsuccessful and Squalo remained in the Varia for the next eight years until Xanxus was freed. Towards the end of the coup, unbeknownst to Xanxus, Squalo overheard him and Timoteo discussing Xanxus‘ illegitimacy.
Squalo first arrives in Namimori after battling Basil all the way to where Tsuna and his Family are dining downtown. He, at that time, does not recognize Tsuna as the 10th Vongola Boss. Yamamoto and Gokudera then step in to aid Tsuna in fighting him, but they are easily defeated by Squalo. Squalo takes Yamamoto on first and deduces that he doesn't know a style because his swings are light. He defeats him by shooting several small amounts of Gunpowder from his Sword into the ground, blowing him up. Next, after Gokudera attempts to bombard Squalo, he quickly slashes the fuses off Gokudera's Dynamite, extinguishing them and leaving Gokudera in surprised shock. He then delivers a harshly punishing kick to Gokudera, rendering him unconscious and unable to battle.
Dying Will Tsuna steps up to square off with Squalo, but he easily catches his opponent's punches while simultaneously realizing who Tsuna truly is. Squalo dexterously holds and beats Tsuna before he can land the finishing blow. Soon thereafter, Dino, the current Boss of the Cavallone Famiglia, steps in to confront Squalo, questioning him on his behavior in fighting against children. Squalo disregards Dino and steals the Fake Half Vongola Rings fleetingly, reluctant to cause even more trouble by fighting an allied Family. He tells Dino that for his (Dino's) sake, he'll leave the children's lives in Dino's hands, and hurriedly leaves.
Squalo delivers the Rings to Xanxus, the Boss of the Varia, as was his task, but Xanxus recognizes them as Fakes sooner than Reborn and the others expected. He appears in most of the Ring Battles as a spectator, as well as a commenter on the Varia's side. Later, Squalo fights Yamamoto in the Rain Ring Battle. Squalo is certain he's going to win when he discovers that Yamamoto fights with a style he has already learned and beaten. But he ends up losing the battle because he does not know the secret of the Shigure Soen Ryu style: it branches off at who their past mentor was to make sure that the style remains strong and undefeatable. In the process, the Techniques may change. Squalo is defeated by Yamamoto's Technique that he added to the Sword Style; Mirroring Rain. Squalo, now unconscious, falls into the water within the Rain stage, where a shark has been released. The watching Vongola and Varia fear the worst and assume that Squalo is dead. Later, in the Sky Battle, Squalo reappears, albeit wheelchair-bound and badly injured with Dino and the Cavallone, much to Tsuna's and his guardians' surprise. Dino reveals that the Cavallone had set up men within the Rain stage to rescue the loser who would fall into the water at the battle's end; Dino states that he had expected Yamamoto to lose the battle and had put preparations in place to save him, but wound up saving Squalo instead. Squalo, in his hospital room, refused to reveal any information about Xanxus and his plans to Dino but, at the Sky Battle, was accepted as a spectator along with Dino and several Cavallone members.
Squalo is seen again during the Future Arc when he takes command of the Varia's core group (minus Xanxus, Gola Moska, and Mammon) with a new member named Fran participating in their Raid in Italy. The group then splits up into Belphegor and Fran, Levi A Than, and Lussuria, and Squalo alone. He encounters some of the lower ranking Varia Members assigned to feed Xanxus and is enraged when he finds out that Xanxus beat them up for not bringing him the right food, but is then momentarily diverted when he senses enemies approaching. He releases his Squalo Grande Pioggia to defeat them.
Squalo later comes to the forefront when he reads a report by Dino and learns that Yamamoto lost to Genkishi. After taking his shark out to sea and boarding a boat that's on its way to Japan, he arrives in the Vongola Hideout with a gift of tuna to Dino, commenting that the security in the hideout is laughable, and then proceeds to viciously attack Yamamoto by kneeing him in the gut who, without his guard up, is easily knocked out. Squalo then carries him off for training.
Squalo decides to come for Choice and hides in the base Shoichi Irie constructed, as such becoming the second known stowaway. It seems that Yamamoto harbors no ill will towards him. During Tsuna's fight with Torikabuto, he notices that Tsuna's Sky Lion is very similar to Xanxus's Sky Lion (they are from the same weapon series).
In a flashback, Squalo is shown trying to persuade Yamamoto to devote himself completely to the sword, because he cannot reach his full potential as a swordsman if it's not his only passion. He does not like Yamamoto's childish behavior in the Future Arc.
After returning to Vongola HQ, he tries contacting Lussuria for backup, though nobody can be sent. The transmission gets cut off by Zakuro's attack. Squalo is able to use his Rain Flames to fend off Zakuro's Storm Flames, and tries to buy time while the others escape. He loses his prosthetic sword hand and is defeated by Zakuro without any difficulty. He is later revealed to have survived. Dino believes Squalo was defeated only because Byakuran has fought them in a parallel world and therefore knows all their techniques, briefing the Real Six Funeral Wreaths on their Abilities, Strengths, Techniques, and how to counter them. He loses his hand, which he threw away for the emperor's sword and understanding of his technique. It is shown when Ghost is absorbing their flames. However, he eventually either regained it or had it replaced.
Later after the final battle with Byakuran, he was talking with Yamamoto before everyone's return to the past by asking was he going to play baseball again and calling him the naive brat. He then leaves with Yamamoto thanking him.
Squalo was seen taking Mammon away with Belphegor after the Mist Inheritance Test in Kokuyo Land.
The Varia appear at the Ceremony except for Xanxus, who Squalo states was absent and wouldn't attend. He and Dino were able to see through Chrome's illusion of Yamamoto, questioned Tsuna about it, and offered their assistance.
During the Simon's attack at the Ceremony, Squalo alongside the other Varia members and Dino were attacked by Adelheid who was using her abilities to prevent them from entering the fight. After the attack, Squalo offered the Ninth the assistance of the Varia in tracking the Simon family, but his offer was refused due to the Ninth not wishing to produce any more victims.
When the Simon's base has been discovered, a meeting is held between the Ninth and Tenth family in which Squalo represents the Varia. Squalo becomes outraged at Tsuna's opinion of Enma's attack, states that the conflict between the two families is a Mafia war, and refuses to accept the idea of the Ninth only sending the Vongola X Guardians and Reborn to the Simon Famiglia Base. However, the Ninth insists on doing so.
Squalo is first seen in the Curse of the Rainbow Arc during the meeting in the Varia's dining room. He is the one who explains to the group that they are going to scout Fran to the Varia as a new officer. Despite vehement objections from every member except Xanxus and Mammon, Squalo goes ahead with the mission. He flies with the rest of the Varia, minus Xanxus, to the secluded region of Jura, France where Fran is rumored to live. They send Mammon to talk to Fran's elderly grandmother, and follow the river like she says in order to find Fran. Squalo and the others ascend the cliff face, commenting on how it was impossible for a normal to be able to reach a place such as that. At the top, they come face to face with the Kokuyo Gang. Bel spots Fran first, and they all watch as he notices their presences. However, Fran mistakes the Varia for tooth-decay fungi and Mukuro's gang for fairies, then runs in fear of them after Bel attempts to kill him.
Squalo and Mukuro corner Fran with their sword and trident respectively, and begin interrogating him. Squalo is the first to realize that Fran might have amnesia, and questions the child to affirm this. He and Mukuro each suggest simultaneously that the other take Fran, and the situation devolves to a game of Ladder to decide custody, until Fran stands from the river and asks if it is ok for him to choose his own fate, pointing to one of the two groups. It is eventually revealed that Fran chose Kokuyo. Later, after Mammon requests Xanxus and Varia to fight on his behalf, Squalo is briefly seen walking in Japan along with the other main Varia members, with Dino watching them. The Varia end up staying at the same hotel as Dino and the Cavallone Famiglia. Squalo and Dino briefly encounter each again in the hotel's dining room when the Varia are having dinner, and Squalo addresses Dino, dryly remarking that it would be nice if they could just have a quiet meal.
On the first day of battle, the Varia encounter and start fighting Enma, at the time Skull's sole representative. The battle is one-sided, with Enma sustaining much damage as the Varia show off the strength of their new rings. They, at last, prepare their killing blows to finish off Enma. Skull desperately tries to save Enma and yells "Present!" in order to release his Arcobaleno curse for a short time, returning to his full-power adult form. Skull, in his full strength, defends Enma from the Varia's killing shots with Undead Body. Squalo and the Varia are surprised by this, but are unable to do anything more because the 10 minute battle ends right then. They leave, swearing to finish off Enma the next time they meet.
At the start of the second day of battle, Squalo and the Varia encounter Hibari and Fon. The two teams are surprised to meet each other, but prepare to fight anyway. Squalo's battler watch is destroyed by Fon, leaving only Xanxus and Mammon to fight Hibari and Fon. At the end of the battle, Hibari destroys his boss watch, disqualfying his own team from the representative battle. Xanxus intends to do the same, but Squalo, along with the other Varia members, stops him. Shortly after, the Vindice appears and heavily injures all of the Varia members, though Squalo is still able to fight using the spare watch. When the third battle starts, Mammon helps his team to escape using his remaining curse release time.
On the fourth day of the battle, Squalo, Xanxus, Mukuro, Dino, and Byakuran confront Jaeger and Bermuda, stopping them from helping Small Gia and Big Pino. They are shocked to witness the strength of Jaeger, who then cuts off Xanxus' right arm. Squalo immediately attacks Jaeger once he realizes this, but Jaeger easily dodges, shatters Squalo's sword and stabs through his chest, rendering Squalo unable to fight. Soon after the battle, Mammon replaces his pierced heart with an illusion temporarily until they can find a heart fit to transplant. It is unknown if the latter charged him or not. Xanxus makes him run back and forth several times, making him out of breath when he stops to speak to Tsuna, who asks if he's all right. Squalo is present when some of the characters get into a fight and damage the hospital facilities.
He is last seen with the other Varia members when Tsuna thinks about the people he (Tsuna) can rely on.