Sakura Note is set among two towns and their surrounding countryside. The player takes control of the protagonist, who is an average, fifth grade boy. A girl named Nanami Yoshida has just moved into his neighborhood, but she happens to be targeted by a local gang of ghosts. This is somehow connected to a pair of cherry blossom trees set among the two towns, one of which is withered and dying, while the other blooms lively. The protagonist decides to seek out the truth of both mysteries by speaking with the inhabitants of the villages.