D.Gray-man follows the adventures of 15-year-old Allen Walker ,whose left arm can transform into a monstrous claw and destroy Akuma, evolving machines created by the Millennium Earl to help him destroy humanity. As ordered by his master General Cross Marian, Allen becomes an Exorcist,people who can destroy Akuma, for the Black Order, an organization attempting to stop the Earl. He becomes a powerful asset for the Order because he can detect disguised akuma with his left eye. Allen is sent to recover pieces of Innocence, a substance that gives the Exorcists the ability to destroy Akuma. The Earl decides to call together the Noah Family, superhuman descendants of Noah who can destroy Innocence. Both sides start the search for the Great Heart, the most powerful piece of Innocence that will assure victory to the side that finds it.

During his search, the Earl begins killing the Generals, the Order's most powerful Exorcists. To protect them, the Order attempts to bring the Generals back to headquarters, and Allen and three other Exorcists are sent to search for the missing General Cross. During the search, Allen and Lenalee Lee are nearly killed and saved by their Innocence, leading the Earl and Bookman and his apprentice Lavi , who are chronicling the war, to believe one of them possesses the Great Heart. Meanwhile, the Order learns that the 14th, a Noah that betrayed and was killed by the Earl, implanted his memories into Allen. The memories will erode Allen away until he becomes the 14th. This leads the Order to believe that Allen may betray them.