Lucky Star‍ '​s story mainly portrays the lives of four Japanese girls attending a Japanese high school. The setting is mainly based on the city of Kasukabe in Saitama Prefecture.^[3] The main character is Konata Izumi, a lazy girl who constantly blows off her schoolwork and homework, and instead uses most of her time to watch anime, play video games, and read manga. Although she is lazy, she has also proven to be very intelligent and athletic.

The serialization began with the four main characters in their first year of high school: Konata Izumi, Kagami Hiiragi, Tsukasa Hiiragi, and Miyuki Takara. As the story progresses, they move on to their second and third years. However, the anime starts the story with them beginning their second year, and the other high school girls that are seen in the opening are only introduced halfway through the series. The storyline usually includes numerous references to popular past and present manga, anime and tokusatsu series.

The spin-off manga, Miyakawa-ke no Kūfuku, focuses on the daily lives of two sisters, Hinata and Hikage Miyakawa, who live an impoverished life due to Hinata's wasteful habits.