The main part of the story takes place at a high school in Japan. There is a "secret of this world" that Kyousuke speaks of; Kengo and Masato are also aware of this. The characters live in either the male or female dormitories on the school grounds which are adjacent to each other. Facing the dorms is the main school building where classes take place which also houses the cafeteria on the ground floor. The school is four floors tall and offers a roof that anyone can go up onto if they wish. Beyond the main school building is the large schoolyard, with the pool area adjacent to the yard. On the other side of the field, is the baseball field, with the gymnasium and tennis court beyond it which is closer to the main school building.
Childhood and adolescence are two important themes in Little Busters! The opening video of the visual novel starts with two lines written in English: "What 'Adolescence' do you have?" and "Do you remember 'Childhood'?". Riki Naoe, the male protagonist, has four childhood friends whom he grew up together with through adolescence and still hangs out with when the story begins. Thus, friendship is another theme presented in the form of Riki's relationships with his friends in high school, and is thought to be irreplaceable. The opening video of the original visual novel contains a third line written in English, "The irreplaceable one existed there," though another line was added into the opening video of Little Busters! Ecstasy: "This will remind you that you have to recollect 'Adolescence'."