Katawa Shoujo is a bishoujo-style visual novel set in the fictional Yamaku High School for disabled children, located somewhere in modern Japan. Hisao Nakai, a normal boy living a normal life, has his life turned upside down when a congenital heart defect forces him to move to a new school after a long hospitalization. Despite his difficulties, Hisao is able to find friends—and perhaps love, if he plays his cards right. There are five main paths corresponding to the 5 main female characters, each path following the storyline pertaining to that character.

Hisao Nakai
Troubled over his months-long stay at the hospital after his heart almost gave out and trying to adjust to his new surroundings, he is trying hard to find his place in the world. After being thrown into a new beginning, the chaotic circumstances have forced Hisao to rethink his apathetic disposition, especially regarding things like life, friendship and future.

Emi Ibarazaki
Despite being left with legs amputated below the knee, Emi is perhaps one of the most cheery, happy-go-lucky girls on the entire globe, let alone the school. Not one to be left in despair even after the accident that claimed her legs, Emi views her disability more as a blessing, her prosthetic legs having brought her to the heights of her ability on the track team rather than becoming a permanent obstacle.

Hanako Ikezawa
At a young age, Hanako had a traumatic experience that left her life in shambles. Her father died when their home burned down in an accident, which also disfigured Hanako herself permanently. She is reclusive to the extreme, shunning from all other people to the point of actually panicking from any social contact. Her only trusted friend is Lilly, who has taken Hanako under her wing ever since the two were introduced to each other.

Lilly Satou
Blind since birth, Lilly is caring, responsible and friendly - the perfect foil to Hanako, her best friend, whom she shares an almost mother-daughter relationship with, in addition to her free time often being spent drinking tea alongside her companion. In class she is a diligent student, with her sense of confidence serving her well in her role as class representative of class 3-2.

Rin Tezuka
Since Rin’s arms are tiny stumps due to a severe birth defect and subsequent surgery, she uses her feet and occasionally her mouth to do everything, which includes painting. Because of her disability, using skirts is tough, so Rin is wearing a boy’s uniform at school. Her creativity is matched by her philosophical streak: Rin is fond of occasionally getting lost in thought and giving voice to abstract ideas about man, the universe, and other things that thoroughly confuse people.

Shizune Hakamichi
Strong willed and forceful, Shizune is definitely the leader type. She’s been the class rep, despite being deaf and mute, for as long as her class has had one, and generally takes charge in just about any situation she’s placed in. Shizune is known around the school as a fearsome taskmaster, and skilled manipulator, but also as a fair and just leader.

Shiina "Misha" Mikado
Misha is the interpreter for Shizune and a fellow member of the student council. Cheery, playful, and never one to pull a punch, she happily joins in Shizune's attempts to get Hisao onto the student council.

Akira Satou (Waifu)
The older sister of Lilly Satou. She is also Lilly's guardian in Japan, due to Lilly's parents being absent. She normally dresses in a suit. She has a very tomboyish, carefree attitude, seeming to be a foil to Lilly herself. Rather irresponsible, she made Lilly do most of the cooking while they lived together, and evidently introduced her to alcohol. It is unclear whether or not her minor addiction was the spawn of Lilly's personality, or Akira's support in her drinking.