Agatha Christie: The ABC Murders is based on the novel of the same name. The main character, Hercule Poirot, investigates a serial killer who bases his murders on the alphabet and sends taunting letters to Poirot. This game is set in various English locations, different from other Agatha Christie works.
The majority of the game involves investigating crime scenes and locations, searching for clues by clicking on hot spots. The player often views a close-up view with the number of hot-spots highlighted. When observing people or places, the player must find corresponding spots that match Poirot's statement. During conversations, the player chooses to stay in character for information and bonus points.
Sometimes during the case, Poirot enters deduction mode, using a mind-map to combine collected evidence and form conclusions. This mechanic is similar to Crimes & Punishments: Sherlock Holmes, but with no option to fail. The game also features reconstructions, where the detectives rebuild a timeline. The player must choose how the movie continues at certain points, and an incorrect choice sends them back to the beginning.
The game includes logic puzzles on a separate screen, mostly similar to The Room. These involve manipulating objects by holding buttons or moving parts, revealing hidden mechanisms. Other puzzles compare letters to see if they were typed on the same typewriter. Some inventory puzzles are included, such as combining found keys on locks.