奥村磷（冈本信彦 配音）自幼被神父藤本狮郎（藤原启治 配音）收养，某一日，磷发现了自己其实是撒旦之子的秘密，之后养父的惨死让磷下定居心走上了驱魔师的道路。磷所存在的世界被分为“物质界”和“虚无界”两大空间，人类生存于物质界，在虚无界中，则徘徊着凶残暴戾的魔鬼。
身边接连发生的伤害事件让磷逐渐发现，某些虚无界的恶魔，趁虚而入潜入了人类世界。为了伸张正义保护同类，磷果断的担负起了驱魔的职责。在弟弟奥村雪男（福山润 配音）的帮助下，磷不断的向着真相前进，此时的磷也发现，造成这一切混乱的元凶，可能就藏在他们的身边。

Due to an unusual ability to see strange creatures called youkai, Takashi Natsume has never fit in. Over time, he has accepted that no one would ever believe him and has closed himself.

When Natsume accidentally breaks an intangible barrier, he frees Madara—a mighty spirit in the form of a lucky cat. Madara notices that Natsume bears a remarkable resemblance to his late grandmother Reiko Natsume, an outcast girl who created the Book of Friends. It is now in Natsume's possession.

With no interest in its powers, Natsume decides to keep the book for the sake of his grandmother's memories and to protect it from scheming youkai. Therefore, he makes a deal with Madara: he will hand him the book once his time is up, and in turn, Madara will act as Natsume's unofficial bodyguard. With his newfound goal of freeing those Reiko had sealed, Natsume's relationship with both youkai and humans slowly begins to improve.

As with its prequel, Zoku Natsume Yuujinchou is about Takashi Natsume, a boy who has had the ability to see youkai since he was young, and his bodyguard youkai Madara, nicknamed Nyanko-sensei. Natsume attempts to return names written in his "Book of Friends" (which he inherited from his grandmother Reiko) to youkai in his village. Throughout these adventures, he meets some youkai that are friendly, some that want to steal the Book, and some that want to kill him, as Natsume learns about himself and his relationship with these mysterious beings along the way.

10年的时间可以让少年变成青年，可以让性格温顺的乖学生变成脾气暴躁性格别扭的上班族，让很多事情被忘记，但有些事情却永远无法被洗刷掉。10年前的小野寺律（近藤隆 配音）暗恋着学长嵯峨前辈（小西克幸 配音）。得到前辈回应的律本以为就此可以幸福下去了，哪知因为误会让二人分离，一别10年。律被调到了出版公司的漫画部门，而他的上司居然就是当年的初恋对象，虽然姓氏变了，但分明就是当初那人。嘴上说着麻烦死了讨厌死了的律，心里却依然会因为前辈的一点点温柔而心动，难道他阔别10年爱上的人依然还是初恋对象么？一出出有趣又温柔的故事在漫画编辑部展开。
除了律的场合，还有编辑部其他成员的故事，同样精彩。

In Tokyo's downtown district of Ikebukuro, amidst many strange rumors and warnings of anonymous gangs and dangerous occupants, one urban legend stands out above the rest—the existence of a headless "Black Rider" who is said to be seen driving a jet-black motorcycle through the city streets.

Mikado Ryuugamine has always longed for the excitement of the city life, and an invitation from a childhood friend convinces him to move to Tokyo. Witnessing the Black Rider on his first day in the city, his wishes already seem to have been granted. But as supernatural events begin to occur, ordinary citizens like himself, along with Ikebukuro's most colorful inhabitants, are mixed up in the commotion breaking out in their city.