The story revolves around Rin Okumura, a teenager possessing abnormal strength and endurance who, along with his twin brother Yukio, was raised by Father Shiro Fujimoto, an Exorcist. One day, Rin learns that he and Yukio are the sons of Satan, the strongest of all demons. Witnessing Shiro dying to protect him, Rin ends up doing what his guardian asked him never to do: draw the demon-slaying blade Kurikara, which restrains his demonic powers, from its scabbard. From that moment on, Rin not only gains permanent demonic features like fangs, pointed ears, and a tail, but also the power to ignite himself into blue flames that can destroy almost anything they touch.
At Fujimoto's funeral, Rin has an encounter with Fujimoto's friend Mephisto Pheles, who agrees with Rin's wish to become an Exorcist like his guardian to become stronger and to defeat Satan. Rin enrolls at the prestigious True Cross Academy, which is actually the Japanese branch of an international organization dedicated to protect the human realm, Assiah, from demons and other creatures from the demonic realm, Gehenna. Rin takes part in a special Exorcist course, the existence of which is known only by a few. Much to his surprise, he finds that his brother, Yukio, is already a veteran exorcist and becomes one of his teachers. Thus Rin's journey to become an Exorcist begins, accompanied by his brother and his fellow students who quickly become his friends and comrades-in-arms.
世界是由兩個空間組成，像鏡子般地連為一體。有人類居住的物質界，及惡魔居住的虛無界。平常兩界之間無法互相接觸和往來。可是惡魔能憑依於和其性質相似的物質從而進入物質界。虛無界之神撒旦在找尋物質界能承受他力量容器的過程中，認識了一名人類女子並誕下了私生子「奥村燐」和「奥村雪男」。原本對此事毫不知情的燐，在一次事件中「被封印」的力量覺醒和與養父藤本獅郎的吵架中，發現了自己是撒旦私生子的秘密。在此同時，藤本獅郎被撒旦附身，並企圖帶燐返回虛無界。藤本獅郎為了中斷附身並保護燐而選擇自殺。為了不想要任何人再為他犧牲、對自己發誓要變得更強並打敗他的生父撒旦，燐毅然決定成為一位出色的驅魔師，於是燐進入了正十字學院。出乎意料發現，這個學院實際上是一個日本國際組的分部，致力保護物質界。燐參加了一個只有少數人知道的驅魔課程，卻驚訝的發現，他的雙胞胎弟弟雪男已經是一名經驗豐富的驅魔師，並且還成為他的驅魔老師。
