When Sasori was young, hisfather and mother were killed by Sakumo Hatake in battle, leaving him in the care of his grandmother,Chiyo. When Chiyo attempted to cheer him up by teaching him puppetry at age five, Sasori's innate aptitude for the art became apparent, and he even began to devise masterful ways of eliminating a puppet master's weaknesses in battle. His skills even allowed him to create two puppets in the image of his parents in an attempt to discard the terrible loneliness he felt. However, as the puppets were unable to give him the real parental love that he desired, Sasori lost interest in them, and they later fell into Chiyo's possession. Sasori created many other ingenious puppets, includingKuroari, Karasu, and Sanshōuo.

During the Third Shinobi World War, the effectiveness of his puppets in spilling enemies' blood on the sand gave rise to Sasori's moniker "Sasori of the Red Sand". However, motivated by his desire to make works that last forever, Sasori began experimenting to createpuppets out of people. In the anime, his only friend,Komushi, lost his right arm during his border control duty, so Sasori gave him a new puppet arm. After Komushi perished, having accidentally ingested some of Sasori's poison, Sasori proceeded to turn him into one of his first human puppets. Twenty years before his introduction in the series, Sasori left Sunagakure at age fifteen. Over ten years before his own death, Sasori secretly kidnapped the Third Kazekage and made him into one of his human puppets.Sasori receiving intel on Orochimaru from Kabuto.

After joining the Akatsuki, he utilised his skills to create numerous spies likeYūra and Mukade from Suna as sleeper agents. Sasori was paired with Orochimaru, who shared his desire of an everlasting existence. Later, Sasori joined his group in recruiting Deidara into Akatsuki. After Orochimaru left the Akatsuki following his failed attempt to take Itachi Uchiha's body, Sasori bore a grudge towards his former partner and sent Kabuto Yakushi to be his spy in Otogakure. Nevertheless, Sasori was unaware that Kabuto was working for Orochimaru long before he posed as an Akatsuki spy, with him and the rest of the Akatsuki made to think that Kabuto joined Orochimaru's side after being dispelled of Sasori's brainwashing.