Sanosuke joined the Seikihoutai at a young age. However, before becoming one of the youngest members of a group soon to be known as traitors, Sano's last name was Higashidani, and he had originally been living in a quiet town with a population silk waystation called Shinshuu with his parents and younger sister. While his past remains a total blur, what is known is that Sanosuke never could agree with his father. His dad, Kamishimoemon, always disagreed with his son's point of view on things, while his sister, Uki, completely looked up to her big brother.

In the Seikihoutai, Sano looked up to his leader, Sozou Sagara. Even at his age, Sano was loyal to his leader and group until they were terminated by the Meiji Government themselves. From that day and after Sozou's public execution, Sanosuke began wandering around, beating up anyone for fun, just to let out his anger for the government he hated so much.

For years, Sano ventured, finally winding up in Tokyo. Throughout his time spent travelling, he picked up the nickname Zanza because of the heavy sword used for killing horses in battle he carried around called the Zanbatou. On the back of his shirt was the character of 'Aku', meaning evil or bad. He was always short of money, but somehow managed to stay in a flat in a rowhouse.

Never once did Zanza use his fighting capabilities for pay until he was asked by the Gohei Brothers to kill Kenshin. Once they had mentioned that their target was formerly known as Battousai Hitokiri, Sanosuke readied his infamous Zanbatou and went off into battle, not for pay, but to let out his frustration upon one of the men that assisted the most in helping to create the Meiji Government with his sword during the Bakumatsu. During their fight, however, Sanosuke learned that Kenshin was just like Sozou, a man who had a vision to create a Japan where everyone had equal opportunities. After that, Sanosuke finally accepted defeat, and from there on, continued his life not as a street fighter upset at the Meiji Government, but as a companion to Kenshin, assisting him in his battles because of the respect gained from him.

Often, Sano hangs around the Dojo Kamiya, freeloading off of food and Kaoru's money. A choice restaurant for Sanosuke is the Akabeko, the only place in town that allows him to keep a tab and not demand that he pay it as soon as possible.

When he fought Kenshin for the first time, Sanosuke's Zanbatou was broken. Although he later did what he could to repair it, Sano acquired the Futae no Kiwami from Anji in a short learning span of just one week. The only downfall is that Sano can only execute the technique with his right hand. Before that, Sano relied on basic brawling for his arsenal. Though, after using the Futae no Kiwami too often, Sanosuke's right hand became frail. He had gotten it fixed up by Megumi, but foolishly used it in many fights, resulting in constant visits to the foxy doctor. It was not until his return from his hometown that he learned a way to lessen the recoil of the Futae no Kiwami.

It may not seem like it, but Sanosuke has had a great deal of influence on many of the other characters. He was the one who convinced Megumi from committing suicide, encouraged his younger brother Outa to grow strong by learning Kamiya Kasshin Ryuu, and slightly inspired Yahiko to become the man he grew up to be later on in his life.

Sanosuke did make a return to Shinshuu, where he met up with his entire family, excluding his deceased mother, after he had gotten frustrated at Kenshin when he fell into a deep state of depression. He remained a stranger to his siblings until his departure. During his short stay, many things developed. Sanosuke got himself involved in his father's business to protect the town from being taken over by a Yakuza led by the nephew of the Meiji Government's Tani. Because he had not only defied the government, but took out a politician as well, a search warrent was made for Sanosuke. Once Kenshin had defeated Enishi, Sano's whereabouts were discovered about, forcing him to leave Japan for a while and set off for a journey around the world. The last known whereabouts of Sanosuke was in a letter he had written Kenshin and the others all the way from Mongolia.