Gabriel Knight is a wise-cracking bookstore owner and would-be author. He is the last in a long line of Shadow Hunters, those fated to fight supernatural forces of evil. Tormented by terrifying nightmares, he must spend every waking moment scouring the side streets and back alleys of New Orleans for the key to his dark past. One day, a blood-chilling murder shocks the inhabitants of the city. The police detective assigned to investigate the crime is Gabriel's friend. In the beginning Gabriel collects evidence in hope of using the material for his new novel; but soon he finds himself personally involved in the investigation, and plunges deeper into the world of secret societies and murderous cults.

Gabriel Knight: Sins of the Fathers is a third-person puzzle-solving adventure game. Created by Jane Jensen, the game differs from Sierra's Quest games (e.g. Space Quest) by having a realistic setting and focusing (despite its supernatural elements and humor) on mature themes and detective work. In this way it is more similar to the company's earlier Laura Bow games.

The game's icon-based interface is the same as in Sierra's previous titles, with verb commands that allow interaction with the game world and its inhabitants. Though the game still has plenty of inventory-based puzzles characteristic for classic adventure, its gameplay is heavily inclined towards dialogue. Typically, Gabriel will have to interrogate other characters, choosing conversation topics and thus gradually finding clues and advancing towards the mystery's solution.

The game's locations are done in hand-painted style. The CD version of the game adds full voice-overs to the dialogues, as well as narrator's voice to text descriptions.