Gabriel Knight is a writer and owner of St. George's Books, a bookstore in New Orleans. He runs the store with his asistent Grace Nakimura, a 26 year-old with a Master degree in History and Classics.
Grace will research issues that Gabriel has encountered during his investigations.
Gabriel is confronted with a writer's block and he thinks he can solve this problem by focusing on a new subject, a series of voodoo murders in the city.
Fortunately, he has a friend at the police force he knows from childhood, homicide detective Franklin Mosely, who is quite willing to help.
When Gabriel visits his grandmother he discovers his roots as a descendent of a German family. He learns that his grandfather has changed his name and that a man who has been calling him after his frequent nightmares, named Wolfgang Ritter, appears to be a family member.
At a visit to the police station he learns that another murder has taken place, this time at Lake Pontchartarin. When Mosely and Gabriel arrive at the crime scene they meet Malia Gedde, an attractive New Orleans' socialite, who happens to drive by.
Gabriel falls in love with her.
At the scene he discovers a pattern on the ground that he copies in his sketchbook.
At the police station Gabriel uses a trick to borrow Mosely's badge. With the badge he is able to get access to the Gedde estate. After his questions Gabriel starts to flirt with Malia, and as she already knows he is an imposter, he is thrown out of the mansion. At Jackson Square he finds an artist who is willing to complete the partial sketches he has managed to get at the police station.
For his research he visits various locations in the city, for instance the Voodoo Museum with its sinister curator Dr. John, the St Louis Cemetary #1, the Dixieland Drug Store and the "voodooienne" Magentia Moonbeam with her python named Grimwald.
He also visits a Professor Hartridge at the Tulane University, which identifies the pattern as a Voodoo vévé, a religious symbol. Hartridge will examine it and inform him about his results.
From an arrested drug addict Gabriel learns that the murders are connected to a Voodoo cartel. Mosely thinks though that the murders are just "common" gangster murders, and Gabriel has to prove that Mosely is wrong.
When he visits Tulane University again Professor Hartridge has been murdered. After his murder, together with other evidence he has found, Gabriel manages to convince Mosely. Mosely disappears after his visit because he fears the cartel has corrupted the police.
After his visits to his grandma and a phone call with his family member Wolfgang Ritter, Gabriel has learned that all the men in the family were Schattenjäger ("Shadow Hunters") whose task it was to combat the supernatural evils in the world. His grandfather and father have perished at a young age by their efforts, and it seems that he is doomed to follow in their footsteps.
After using a tracking device from Mosely's office on a coffin at Dr. John's museum and getting information about a planned meeting, Gabriel visits a swamp to find out that the cartel is headed by Malia Gedde. She is possessed by a spirit called Tetelo, and Tetelo identifies Gabriel as a witch-hunter. His life is being threatened, but he is saved by Grace who has followed him.
The original Tetelo has stolen a talisman from Gabriel's ancestors that could destroy her. The talisman was hidden with her remains, but Gabriel can't find it in Gedde's family tomb in the city.
When he visits Schloss Ritter, Wolfgang is missing. He learns how to initiate himself as a Schattenjäger, and in a secret library he reads some books that reveal that the remains of Tetelo are hidden in Benin in a snake mound.
In the snake mound in Africa he is confronted with mummies. By using his dagger on one of the mummies Gabriel recovers the lost talisman. He meets Wolfgang and together they manage to enter the inner chamber of the mound. However, Wolfgang is killed in the process, and Gabriel swears to revenge his death.
When he returns to New Orleans, a note from Mali informs him that Grace has been kidnapped. Together with Mosely he succeeds in locating Grace. Using disguises at a ritual that is taking place, Gabriel is confronted with a choice he has to make: saving the life of Malia or acting as a true Schattenjäger