Kimimaro was the sole survivor of the Kaguya clan, a group known for their ferocious and battle-loving nature. He was born as a rare wielder of the Shikotsumyaku, a kekkei genkai that allows the user to manipulate their own skeletal structure. His father, fearing this immense power, kept him locked in a cage for most of his early life, releasing him only when the clan needed him to fight. The Kaguya clan was eventually wiped out when they launched a suicidal attack on Kirigakure, leaving Kimimaro as the only survivor.

After wandering alone, Kimimaro was found and taken in by Orochimaru. This encounter became the defining moment of his life. Orochimaru was the first person who seemed to care for him and give him a purpose, and Kimimaro developed a profound and unwavering devotion to him in return, viewing him almost as a messianic figure or a father. His entire motivation became centered on serving Orochimaru, believing his sole reason for existence was to be useful to the one who rescued him from loneliness. This loyalty was absolute; he sought to protect his master and ensure the continuation of his ambitions.

Unlike the rest of his violent clan, Kimimaro did not possess an inherent love for killing or fighting. He was a calm, quiet, and reserved individual who saw combat merely as a means to fulfill his duty and be of use to others. He demonstrated a sense of honor in battle, once pausing a fight to allow his opponent, Rock Lee, to take his medicine. However, he also showed a deep disdain for what he called trash ninja, at one point plotting to kill his own ally, Tayuya, for failing to complete a mission. He rarely displayed strong emotions, maintaining a serene and collected demeanor even in combat, though he could be provoked to rage if his faith in Orochimaru was insulted.

In the story, Kimimaro was the leader of the Sound Four, forming the Sound Five when he was with them. His combat abilities far surpassed the combined power of the other four members, who feared and respected him. Orochimaru originally intended to use Kimimaro as his next host body, primarily because of his rare and powerful kekkei genkai. However, Kimimaro was afflicted with an unknown, terminal illness that prevented him from fulfilling this role, a realization that brought him to tears as he felt he could no longer serve his master. Despite his failing health, he forced his body to action one last time to retrieve Sasuke Uchiha, who was intended to be Orochimaru's new vessel.

Kimimaro also shared a significant relationship with Jugo, the source of Orochimaru's cursed seals. Kimimaro was one of the few people, and the only one for a long time, capable of suppressing Jugo's uncontrollable homicidal instincts, and they developed a close friendship. Before his final mission, Kimimaro visited Jugo, thanked him for their friendship, and told him that Sasuke was now his legacy.

Kimimaro's notable abilities revolve around his Shikotsumyaku, which he called his Dance of the Larch. For the ultimate technique, he could perform the Dance of the Seedling Fern, where he thrust his entire body into the ground and caused a massive forest of sharp bone spikes to erupt across the battlefield. He was also branded with Orochimaru's Cursed Seal of Earth, which he could activate to enter a second level form that granted him even greater power, changing his appearance to a more demonic, reptilian state. Despite his debilitating illness, he proved capable of simultaneously and successively fighting Naruto Uzumaki, Rock Lee, and Gaara, pushing each of them to their limits and dying only when his illness finally overtook him at the moment of his would-be victory over Gaara.

Later in the series, during the Fourth Shinobi World War, Kimimaro was reincarnated by Kabuto Yakushi using the Impure World Reincarnation technique to fight for the Akatsuki. He was ultimately defeated and his soul was released from the technique when it was cancelled, allowing him to finally return to the afterlife.