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Edward Pierce, a troubled private investigator beleaguered by his time in World War 1, is approached by a stranger claiming that his daughter, son-in-law, and grandson were all killed in a mysterious fire. He has had suspicions of something strange going on with his daughter when he noticed her paintings were taking on a sinister, otherworldly tone. After presenting Edward with one of those paintings, he hires him go to the island of Darkwater, off the coast of Boston, and find out what happened to his daughter. Along the way Edward will discover the terrifying truth of what occurred while crossing paths with bootleggers, superstitious whalers, cults, questionable medical professionals, and eldritch horrors not meant for the eyes of man.
The game is set in first person. The only time this changes is during in-engine cut scenes that are scattered throughout the game. The game mainly consists of the player searching for clues hidden through the levels and conversation systems meant to drive the plot. This can be greatly affected by an RPG system actually taken from the Call of Cthulhu pen-and-paper game, such as using strength to break through a hidden door or medical knowledge to diagnose the cause of death of a character. There are puzzles at various times as well, which can also be hindered or aided by the status of the player's stats. Call of Cthulhu also relies on simplified stealth mechanics but this is not affected by the character's stats. These sections always end in a game over state if the player is caught. Some events in the game can be altered such as not being able to save a character or even deciding how to solve a puzzle. Also, Edward Pierce has the ability to enter into a "detective mode" in certain important scenes that allows him deduce events. This is similar to the detective mode in other games.
Call of Cthulhu does include light RPG elements. This, at its core, is represented in a stylized character sheet in the menus. Most of these statistics are increased by simply playing the game but more points are awarded based on what the player does. The statistics in Call of Cthulhu are:
At specific times in the game the player can open up a detective mode, similar to other games. This allows the player to piece together events that occurred in the past such as a crime scene. The player can only engage in this at specific times opposed to at will.
Call of Cthulhu also provides as many as four different endings depending on the player's actions and dialogue options.