Yuuta Hibiki wakes up in the room of Rikka Takarada and notices two things: he has no memories, and he can hear a mysterious voice calling his name from a nearby room. On further inspection, he finds a robot—which introduces itself as Hyper Agent Gridman—behind the screen of an old computer. Much to Yuuta's surprise, Rikka cannot hear Gridman, nor can she see the ominous monsters looming over a thick fog as it envelopes the town outside. Another giant monster materializes in the city and proceeds to wreak havoc. Amidst the confusion, Yuuta is once again drawn to the old computer and merges with Gridman. Suddenly, he appears in the middle of the battle and is forced to fight the monster. Together with Rikka and fellow classmate Shou Utsumi, Yuuta forms the Gridman Alliance to defeat the monsters plaguing the city and find whoever is responsible for their emergence.

Nozomu Itoshiki is a high school teacher so pessimistic that even the smallest of misfortunes can send him into a pit of raging despair; some of these catastrophes even lead to suicide attempts. Sayonara Zetsubou Sensei is a satirical slice-of-life comedy set in the modern day, covering various aspects of Japanese life and culture through Nozomu and his interactions with his students: Kiri Komori, a recluse who refuses to leave the school; Abiru Kobushi, an enigma who frequently arrives to class with severe and mysterious injuries; the hyper-optimistic Kafuuka Fuura, Nozomu's polar opposite; and several other unusual girls, all of whom are just as eccentric as their teacher.

Makoto Niwa meticulously tallies the amount of positive and negative youthful experiences he engages in as if to grade his own life. When his parents go overseas, he moves to a new town to live with his aunt, welcoming the change and ready for a fresh start. However, as ordinary as he had imagined his adolescence to be, he could never have taken the existence of an enigmatic long-lost cousin into account. Upon moving into his aunt's house, he discovers the cousin he never knew about: Erio Touwa. Despite being Makoto's age, she couldn't be more different: Erio chooses to wrap herself in a futon all day rather than to go to school. She even claims to be an alien, and with a speech pattern and personality to back it up, any chance of Makoto's dreamt-of normal life is instantly tossed out the window. As he meets a string of other eccentric girls in town, Makoto must face the possibility of seeing his youth points in the red. However, he might be surprised by how thrilling an abnormal youth can be.

Traumatized by school, Jun Sakurada spends his days at home as a shut-in, purchasing things online, only to send them back before the free trial period ends. So when a note appears on his desk, asking whether or not he would wind something, he assumes it was something he ordered and carelessly circles yes, changing his life forever. A box arrives with a wind up doll inside, but this is no ordinary toy: after Jun winds her up, she begins walking and talking as if a normal person. With a haughty attitude, she introduces herself as Shinku, the fifth doll in the Rozen Maiden collection, a group of special dolls made by the legendary dollmaker Rozen. These sisters must battle each other in a competition called the Alice Game with the help of a human to ensure victory. The winner becomes Alice, a real girl who is worthy of meeting their creator. As more sentient dolls end up taking residence in Jun's house, and a foe from Shinku's past makes her appearance, Jun's life becomes far more complicated than he ever thought possible.