Natsume discovers that the heirloom "Book of Friends" that his grandmother, Reiko, gave him possesses the names of the spirits she defeated and bound to her will. Assisted by a cat whom Natsume addresses as Nyanko-Sensei (lit. Master Little Meow), Natsume aims to return all of the names to their rightful owners.

Natsume is visited by the village's local god who is currently fading because of the lack of devotees.

Natsume is implored to help spirits who are currently being exorcised. He finds a kindred spirit in Tanuma, a boy who also senses spirits although not as powerful as Natsume.

Natsume's secret is found out by Sasada, the class president, during the "Trial of Courage." She asks for his help to find the spirit that lives in the abandoned school. Natsume denies the fact that he can see anything, but she won't take no for an answer. Meanwhile, the spirit, Shigure, captures the rest of their school mates, in fury of the school being torn down...

Natsume comes across an old ticket in Reiko's belongings and decides to go to the abandoned train station to see why she kept it. There, he meets a slow witted spirit named Santo, who was waiting for Reiko the entire time to go Kiriganuma, to see and make up with his friend, Mikuri, but the trip isn't as easy as it first seems...

Natsume is possessed by a swallow spirit, who wishes to meet a human who once helped her. Natsume agrees to help her and the two grow attached. When Swallow finds the human, Natsume feels bad that she can't actually meet him, but when he hears of a kimono that can turn a spirit into a human for a day, he looks for it.

Natsume goes to a hot spring for a school trip, with an errand from Shigeru to pick up teacups from a near by pottery. While there he meets and helps a little fox spirit, who quickly grows attached to him.

Natsume meets a spirit who used to be friends with a man who could also see spirits, but one day lost this ability.

Natsume meets a popular actor named Natori Shuuichi who can also see spirits, and has a side job as an exorcist.

Natsume is possessed by a sick koto player, whose friend wants her to be able to play one last time.

When Natsume finally has enough of Nyanko's behavior, Nyanko leaves, wandering about by himself and causing trouble.

Natsume is cursed by an evil spirit which is sealed to a tree. Not wanting to trouble his adoptive family, he decided to run away from home.

Tanuma finds out that Nyanko-Sensei is a spirit. Tanuma and Natsume enjoy the autumn festival and previous acquaintances are seen again.

Natsume meets a shrine god in the form of an elderly woman. He is forced to help her return a mirror to a youkai said to bring disaster. The youkai turns out to be Reiko, Natsume's grandmother, who the shrine god only mistook as a youkai. Reiko had lent out the mirror so that the shrine god could save the life of an old tree, but the two parted after Reiko learned that the elderly woman was a youkai.

Tanuma's father leaves on a trip and a strange youkai invades his house, spreading miasma that makes all the nearby youkai suffer. Natsume tracks it down and discovers that the noxious youkai was once a resident in an all-youkai village. A portal had opened for a short time during a human ceremony that he had taken his sister to watch. However, they became trapped in the human world, and his sister died. After returning to the old temple where the ceremonies were held, the portal opens and he returns home.

It's Shigeru's birthday and Touko has asked Natsume to buy some strawberry shortcakes to celebrate. However, Shibata, an old classmate of Natsume's, finds him and asks for his help. He remembered Natsume used to say weird things, so he wanted to know if a girl he's been seeing is real or not. When Natsume meets the girl, Murasaki, she seems normal. He reassures Shibata that she is a human. Natsume later has a vision that reveals her to be a tree youkai with intention to eat Shibata. Natsume tries to warn Shibata, he refuses to listen and accuses Natsume of lying. Natsume tries to talk to Murasaki, but she does not waver. It is then revealed that although she had initially planned to eat Shibata, she fell in love with him as they spent time together, and because her tree has been cut down, she will die soon anyway. Shibata receives a note from Murasaki just in time for the two of them to spend her last moments together.

Summer has arrived for Natsume and his friends in the school. After exams, Natsume, Sasada, Nishimura and Kitamoto go on a trip to an art museum. Upon his return, Touko reminisces about an old friend that she felt she'd wronged, this makes Natsume think back to his own turbulent childhood. In the present day, a youkai living in the branches of a tree thinks back to Natsume. She had been bored because no one could see her, and when she found out that Natsume could see youkai, she often scared him to be noticed. Both of them parted ways on bad terms. The story returns to Natsume in the present day, who makes a stop at his old neighborhood to visit the youkai. The youkai, who had isolated herself from humans, is relieved to see that Natsume is okay and has found a reason to smile. The episode ends with Natsume's thoughts, "If there is somebody that you wish to meet, then you are not alone anymore."

Natsume and Tanuma take shelter under a roof from the rain. As it turns out, the house belongs to Taki, and they work together to clean her warehouse where her grandfather studied youkai. Natsume accidentally breaks a seal that Taki's grandfather made to trap a dangerous kimono youkai. The three of them race around the house to find its misplaced limbs before the youkai does--its power will be returned upon completing its body. Natsume and Taki try to get the resident youkai to help, but they refuse. When the kimono youkai comes close to hurting Natsume, they come to the rescue. After Taki thanks them, they all reminisce about their fondness for Taki's grandfather and leave elsewhere.

Natsume accidentally bumps into a woman with blood covering her body. He follows the bloody footsteps that the woman left and discovers a small house. When he opens the door, he sees badly injured youkai. There is someone killing youkai for blood, and with the help of Natori, Natsume tracks down who he believes to be the murderer: Matoba. However, Matoba captures him.

Natsume finds out who's been stealing the youkai blood: the exorcist Matoba Seiji. He investigates with the help of Natori, but is captured by Matoba's servant youkai. Matoba is willing to sacrifice any number of youkai for his own ambitions. He tells Natsume why he's gathering blood: to release the seal on a powerful youkai. Natsume learns that there are people who treat Youkai in a totally different way than he or even Natori.

Natsume is invited to go to a pottery classroom with Shigeru. It's being held in an inn where he once stayed. When he goes there, he meets an old friend: the young fox child he once saved.

Because of his poisonous arrow wound, Madara spends most of his time sleeping to heal. Without Sensei to protect him, Natsume has to remain constantly on guard. Especially since a strange stone seems to stir strange phenomena everywhere around him. To make things worse, it's the cultural festival and Natsume is appointed to serve the clients at the bazaar set by his class. But the pressure of keeping secrets from his friends is causing Natsume to break.

An event in the forest causes Tanuma to avoid Natsume the following days, which he becomes concerned about. Mirrors are mysteriously breaking around the school and one day Natsume catches Tanuma acting weirdly. It turns out that Tanuma has been possessed by a youkai looking for her mirror, which had been broken into pieces during a storm a few days before. Using him as a vessel until she reclaims her mirror, Natsume has no choice but to help her. The youkai warns that there may be others seeking the mirror.

Because of his possession, Tanuma is able to see the youkai around him and thus better understand how Natsume lives.

When a dangerous youkai from Natsume's past finds his current home, he comes down with a fever and dreams about his life right before moving in with the Fujiwaras.

Natsume spends time playing games with youkai he has befriended. He remembers games he was left out of as a child.