Rentarou Aijou holds a painful record: by the time he enters high school, he has already been rejected by one hundred different girls. Desperate for a change in his romantic fate, he prays at a local shrine, where the God of Love appears with a startling explanation. Due to a divine clerical error made at Rentarou's birth, he is not destined for a single soulmate but for one hundred of them. The god delivers a dire warning: if Rentarou meets any of these fated individuals and fails to reciprocate their feelings, they will die from heartbreak.

Faced with this impossible situation, Rentarou resolves to embrace his unusual destiny with total sincerity. Rather than a passive or indecisive protagonist, he is proactive, earnest, and surprisingly competent at building genuine relationships. His goal is not just to date one hundred girlfriends but to ensure every single one of them is truly happy, forming what the group comes to call Rentarou's Family. The series follows his life at Ohananomitsu University High School, an institution with affiliated middle and university levels where most of the story takes place.

From the first day of school, Rentarou's journey begins in earnest as he meets his first two soulmates simultaneously. Hakari Hanazono is a beautiful and wealthy honor student who appears prim on the surface but harbors a deeply perverted and scheming side. Karane Inda is a classic tsundere with a headstrong and aggressive personality who struggles to express her genuine affection. Their rivalry and eventual friendship form the core of the early group dynamic. Soon after, Rentarou encounters Shizuka Yoshimoto, a shy and mute librarian who communicates by pointing to passages in her favorite books. Rentarou helps her by transcribing her beloved novel into a text-to-speech app on her phone, giving her a voice. The fourth girlfriend, Nano Eiai, is an emotionless genius obsessed with efficiency, who initially views love as a waste of time before learning to embrace her feelings. The fifth is Kusuri Yakuzen, a cheerful 18-year-old chemistry prodigy who looks like an 8-year-old due to a failed immortality drug, and she frequently causes chaos with her experimental inventions.

As the series progresses, the cast expands to include Hahari Hanazono, Hakari's wealthy 29-year-old mother, who initially tries to separate Rentarou and her daughter but falls for him herself after he breaks into her mansion to rescue Hakari. She then buys the school to stay close to him. Other notable girlfriends include Kurumi Haraga, a perpetually hungry middle schooler who becomes irritable without food; Mei Meido, Hahari's blind but supremely loyal maid; and Iku Sutō, a baseball-loving masochist who enjoys the pain of intense training.

Several notable narrative arcs define the series structure. One of the earliest and most significant is the Hakari Rescue Arc, where Hahari threatens to send her daughter away to a distant school. Rentarou and his first five girlfriends band together to infiltrate the Hanazono mansion, leading to a dramatic confrontation where Hahari becomes the sixth girlfriend. Another recurring theme involves Karane's struggle with her tsundere nature. In one arc, she loses her ability to be a tsundere, and Rentarou and the other girlfriends work to help her reclaim an essential part of her personality rather than force her to change. Shizuka's backstory is also explored, revealing that her muteness stems from childhood abuse by her mother, giving emotional weight to her character beyond the comedic premise. The anime covers these arcs across its first two seasons, which aired from October to December 2023 and from January to March 2025 respectively.