Black Zetsu was created by Kaguya Ōtsutsuki shortly before she was sealed as the Ten-Tails by her twin sons, Hagoromo and Hamura. In the anime, Black Zetsu would approach Indra alone periodically, goading him with praises and curiosity towards Indra's true potential, even going so far as to say he could rival if not surpass the Sage of Six Paths himself. When Hagoromo later named his younger son, Asura, as the new leader of Ninshū, Black Zetsu tempted Hagoromo's elder son, Indra, to go in war with his younger brother. It decided that Indra's descendants, the Uchiha, would be the main cast of the shinobi history it was creating and also modified Hagoromo's tablet to claim that among other things; the  Infinite Tsukuyomi would be the Uchiha's salvation. Over the centuries, it manipulated the two brothers' reincarnations in an attempt to get one to awaken the Rinnegan, and also recorded many events for Kaguya, including Madara Uchiha and Hashirama Senju's last fight at the Valley of the End.

When Madara had seemingly created White Zetsu and its clone siblings, it was actually Black Zetsu pulling the transformed humans from Kaguya's Infinite Tsukuyomi out of the Demonic Statue of the Outer Path, merging them with the essence of the Hashirama plant clone Madara created to give them a diluted Wood Release.[4] When Madara was on the verge of death, he believed he had created Black Zetsu by imbuing his will into half of White Zetsu, and that the complete Zetsu was partially his clone. Zetsu later accompanied Obito Uchiha to Amegakure to locate Nagato, who had unknowingly been given Madara's Rinnegan as a child, and watched as Obito introduced himself as Madara Uchiha.