Atelier Totori takes place 5 years after the previous game, Atelier Rorona. It begins with Totori in the fishing village of Alanya, her hometown, and ends after five years pass. Totooria Helmold is Rorona's student who is looking for her missing mother. After the events of Atelier Rorona, Rorona has been traveling across Arland teaching alchemy. One day, Totori and her older sister find a starving Rorona collapsed on their doorstep. She teaches Totori about alchemy, adopting her as a student. Since then, Totori has been learning alchemy on her own.
Everyone in Alanya believes that Totori's mother is dead. However, Totori thinks she is still alive, so she travels to Arland in order to become an adventurer and search for her. Players follow Totori on her journey exploring the world, improving her alchemy, and searching for her long-lost mother.