Lucky☆Star follows the daily lives of four cute high school girls—Konata Izumi, the lazy otaku; the Hiiragi twins, Tsukasa and Kagami (sugar and spice, respectively); and the smart and well-mannered Miyuki Takara. As they go about their lives at school and beyond, they develop their eccentric and lively friendship and making humorous observations about the world around them. Be it Japanese tradition, the intricacies of otaku culture, academics, or the correct way of preparing and eating various foods—no subject is safe from their musings.

Tightly clutching his Gibson guitar, Mafuyu Satou steps out of his dark apartment to begin another day of his high school life. While taking a nap in a quiet spot on the gymnasium staircase, he has a chance encounter with fellow student Ritsuka Uenoyama, who berates him for letting his guitar's strings rust and break. Noticing Uenoyama's knowledge of the instrument, Satou pleads for him to fix it and to teach him how to play. Uenoyama eventually agrees and invites him to sit in on a jam session with his two band mates: bassist Haruki Nakayama and drummer Akihiko Kaji. Satou's voice is strikingly beautiful, filling Uenoyama with the determination to make Satou the lead singer of the band. Though reticent at first, Satou takes the offer after an emotional meeting with an old friend. With the support of his new friends, Satou must not only learn how to play guitar, but also come to terms with the mysterious circumstances that led him to be its owner.

Tomoya Aki, an otaku, has been obsessed with collecting anime and light novels for years, attaching himself to various series with captivating stories and characters. Now, he wants to have a chance of providing the same experience for others by creating his own game, but unfortunately, Tomoya cannot do this task by himself. He successfully recruits childhood friend Eriri Spencer Sawamura to illustrate and literary elitist Utaha Kasumigaoka to write the script for his visual novel, while he directs. Super-group now in hand, Tomoya only needs an inspiration to base his project on, and luckily meets the beautiful, docile Megumi Katou, who he then models his main character after. Using what knowledge he has, Tomoya creates a new doujin circle with hopes to touch the hearts of those who play their game. What he does not realize, is that to invoke these emotions, the creators have had to experience the same feelings in their own lives.

After the destruction of their hometown, childhood friends Kafka Hibino and Mina Ashiro make a pact to become officers in the Defense Force—a militarized organization tasked with protecting Japan from colossal monsters known as kaijuu. Decades later, the 32-year-old Kafka has all but given up on his dreams of heroism. Instead, he cleans up the remains of the slaughtered kaijuu after they are defeated by valiant soldiers—including Mina, who has successfully achieved their shared goal. Upon meeting his new coworker, Reno Ichikawa, Kafka faces a mirror of his past self: an ambitious young man whose one desire is to fight as a member of the Defense Force. Unfortunately, the two are soon involved in a freak encounter with a rogue kaijuu. Though Kafka demonstrates his innate heroic nature and rescues Reno from certain doom, he is left gravely injured. While both men recover in a hospital, Kafka is seemingly attacked by another one of the beasts. As a result, he gains the ability to transform into a humanoid kaijuu with the strength and powers of the massive monsters menacing Japan. Dubbed Kaijuu No. 8 by the military, Kafka resolves to use his newfound gifts for the greater good. Tied together by mutual respect, Kafka and Reno set out to join warriors like Mina at the forefront of the Defense Force.