The story takes place in the year 1920 in the United States of America. Paid to exterminate demons, Chrno and Sister Rosette are professional exorcists from the Magdala Monastery. They travel between various places to prevent demons from taking possession and haunting various things that come from outside the U.S.A.

One day, Rosette was given the orders to investigate a "demon master" known as Ricardo who was a wealthy American. Infiltrating the hotels that Ricardo possessed, they meet a young girl named Asmaria who was captured by him. She had a special power that allowed her to get near gods using her singing. As her power got discovered, it meant people around her always felt uncomfortable. And so, she was always alone.

Seeing how Asmaria was giving up because of her fate, Rosette reassures her and says, "If you give it all you''ve got, you''ll be able to change anything for sure." Their battles were extremely fierce but, thanks to Asmaria''s help, they manage to beat the treachery that stood before them.

Thinking that they''ll have peaceful days again now that Asmaria''s case was solved, some important information comes in. The enemy who was sending out the demons is Joshua. Joshua was the name of Rosette''s younger brother who she was seperated from at birth. In the orphanage where they were brought up, they were well known for how well they got along. Just like twin brother and sister.

But, as Joshua has a power that makes him act as an agent for god, he was also feared by those around him. He longs to go against Rosette for the great power she possessed... And so, Joshua entrusts himself to the great demon Ion and disappears right before Rosette''s eyes. Later, he appears once again to confront them at the monastery. In order to rescue Joshua, Rosette sets off on a journey together with Chrno and Asmaria.

On their journey, as the Rosette party exterminate demons as pros to earn money, they meet Stella. Thinking that Chrno may have been the demon who murdered his parents, she approaches them. However, he finds out that Chrno hadn''t done anything like that in the past and so, she goes along with them so that she could gather information on the demon she''s after.

During that time, the assasins that Ion sent out found them. Being seperated from her friends, Rosette must fight alone. She bearly wins the battle but, in the end, she continues her journey without obtaining any clues linked to Ion...