Nezuko grew up on a mountain alongside her older brother, Tanjiro, and the rest of her siblings and mother, as the eldest daughter of the Kamado family. She presumably took care of her younger siblings as an assistant to her mother, as is briefly witnessed prior to her family's death. Unlike Tanjiro, who was responsible for selling firewood in town, Nezuko would usually help out around the family home.
The family was somewhat poor and, as a result, Nezuko sometimes had to go without things like new clothes in order to ensure that the rest of her siblings had enough food to eat. She did not appear to view this as a burden, and instead was simply just content with helping her family.
After a Demon attack kills almost her entire family, Nezuko is turned into a Demon by the orchestrator of said attack, Muzan Kibutsuji. At first, she is rather wild and even attacks her single remaining brother, however she quickly comes to her senses and swiftly jumps in to defend him from Giyu Tomioka when the Hashira tries to harm him.
Following her awakening after their short fight and her brother receiving instructions from Giyu to find a man named "Sakonji Urokodaki," Nezuko is taken by Tanjiro to first bury and pay their respects to their deceased family. She then hides in a nearby cave, since the sun has risen, and waits for her brother to find something to carry her in so they can travel by day.
The two begin to travel towards Sakonji's home, but run into a Demon, who has just killed and is preying on a family, on their way. Tanjiro attacks the Demon, hitting it in the jaw with his axe, but it swiftly heals the wound and boasts about its regeneration abilities. Angered, the Demon pounces on Tanjiro, but Nezuko swiftly kicks its head off, also kicking its body away as it continues to attack. The pair manage to fend off the Demon, pinning its head to a tree and throwing its body off a mountain, until Sakonji suddenly appears and informs them that they cannot kill a Demon through these methods.
Tanjiro hesitates to deliver the final blow, and, eventually, the sun rises, causing the Demon to disintegrate and Nezuko to flee to the safety of the house.
Nezuko then sleeps for the full two years Tanjiro spends training, not even awakening after he leaves for the Final Selection. Sakonji keeps her in check the entire time, until Tanjiro successfully passes the Final Selection, because it is only then, when he returns to them, that Nezuko awakens. She greets Tanjiro, embracing him and relieving him of his fears.
Nezuko accompanies Tanjiro to his first mission, where she emerges from her box to fight a copy of the Swamp Demon. She falls asleep after the Demon is defeated.
Nezuko spends most of this arc in her box, as it takes place during the day.
Nezuko takes part in the battle against Lower Moon Five, Rui. She helps her brother at first using herself as a shield against Rui's threads but then is captured and tied up by him to the top of several trees upside down, falling asleep as a result of blood loss. Her mom's spirit asks her to wake up and help Tanjiro for saving him from Rui. She wakes up for a moment and deal the killing blow with her newly awakened Blood Demon Art, thanks to her blood that stained on Tanjiro's sword previously and through the same threads that Rui used to tie her up for defending against Tanjiro last attack instead.
After that fight, Shinobu tried to stab her with poison but her attack is blocked by Giyu. Tanjiro tried to escape with Nezuko from the scene, but he fails after Kanao (without being seeing by him) stomps on his back. Tanjiro asks Nezuko to run and his jaw ends broken after a kick on his head. Nezuko proceeds to turn into a small child make a run for her life. Before Kanao cuts a cornered Nezuko head off, a crow appears ordering to bring the Kamado brothers to Demon Slayers' headquarters. She decided on getting to headquarters inside her box.
She is awakened by Sanemi, who stabs her in an attempt to provoke her and her brother. Sanemi trying to prove that Nezuko is dangerous, uses his marechi blood as a bait. Nezuku recalls her family and refuses to drink it at the end. She ends up piss off at Sanemi after being awaken and stabbed. She is carried out to the Butterfly Estate alongside her elder brother.
Nezuko spends almost the entire arc sleeping to recover her strength after she used her Blood Demon Art for the first time against Rui on Natagumo Mountain. Zenitsu tells her about their breathing holding training and then promises her to take her at night where the flower he's holding was blooming. Moreover, he took the goldfish bowl from Shinobu's room without asking and shows it to Nezuko. Later, Aoi found him and chewed him out thoroughly.
Nezuko gets out of her box, only to get confused by Kyojuro Rengoku, whom is strangling a human while he's asleep. She tries to wake her brother up for a head pat and then proceeds to give him a headbutt in frustration when she is unable to rouse him. However, due to Tanjiro's comically hard forehead, she ends up splitting her own forehead open and starts bleeding. This causes her to cry and use her Blood Demon Art on his brother. She uses it on the ropes of the Demon Slayers after they were put to sleep by Lower Moon One, Enmu. She fights with her fingernails since she'll fall asleep pretty soon if she uses her blood. She's helped by a sleeping Zenitsu whom declares he will protect her, which she looks on in awe. Her admiration is quickly dispelled however, as he pops back asleep mid sentence and begins to snore. Both of them defend three cars of the train from Enmu.
After the train is stopped and during the fight between Kyojuro and Akaza, she falls asleep on the arms of Zenitsu who is asleep as well. Before Kyojuro dies, he finally acknowledges Nezuko as a member of the Demon Slayer Corps since she protected the humans on the train. Zenitsu gets her into the box to protect her from the sunlight.
She awakens to her berserk-like Demon Transformation ability during the fight with Daki, the female half of Upper Moon Six. After almost consuming a human in her animalistic state, she is subdued by Tanjiro and is sidelined for the rest of the fight. She proves instrumental in saving several Demon Slayers from the brink of death by using her Blood Burst ability to burn the lethal poison of Gyutaro, the male half of Upper Moon Six, out of their blood.
Nezuko almost disintegrates in the sunlight, but then suddenly becomes a Demon immune to the sun, something which Muzan had tried so hard to find. She assists Genya as they fight the Upper Moon Four, Hantengu.
Nezuko, appearing to have sensed something, gets up. As Sakonji asks the girl whats wrong, she dashes into the forest, seemingly aware of and drawn to Tanjiro's impending death. Kiriya, worried and wondering what to do, yells for her to be retrieved. Kiriya then remembers his father's words to let Nezuko do as she pleases, allowing her to leave. Urokodaki still chases her but Nezuko is far too fast for him. She then leaps off of a cliff, landing safely in the forest below. As Nezuko rushes towards the city, she begins to undergo drastic changes. Her right eye becomes that of her human self, and her hair has returned to being solely black. Nezuko remembers Muzan slaughtering her family, and becomes enraged. She then remembers how Tanjiro carried her through the snow, panicked and desperate, trying to save her life. She recalls every ally and friend she has made along the way and every tender moment she shared with them, including Sanemi stabbing her. As her reversion continues, her hands have now become human. She envisions Tanjiro holding his hand out to her and his promise to protect her, as she becomes fully human once more.