Koichi once lived in a happy and somewhat rich family. He was only a boy when his father decided to stop the running train by himself. Koichi's mother died of cancer, and he got separated from his older brother Eiichi. Ten years have passed since that moment. One day, Eiichi, now wealthy and powerful, returns, telling Koichi that the man responsible for their father's ruin was Shoji Okamura. He plans to destroy Okamura family entirely, and he buys Koichi a house nearby, telling him to gain their trust in order to create a perfect timing for his revenge.

However, Shoji Okamura ran away, abandoning the house along with his daughters. The eldest one had to leave college and get a job in order to support her sisters, and the whole family was beginning to sink deeper and deeper into debts. Eiichi is planning to punish the sisters for their father's sins, but Koichi's feelings begin to change as he gets to know them better, and the moment is nearing when he will have to choose between his brother and the Okamura sisters.

Three Sisters' Story is an adult Japanese-style adventure game. Locations are presented as still screens viewed from first-person perspective. Interaction and navigation are entirely menu-driven and are performed by selecting verb commands and combining them with objects from a list. It is often necessarily to go through commands several times to trigger the next event; some choices, however, may branch the plot, affecting the game's ending.