Famous detective Hercule Poirot is called back from Istanbul to London on urgent business. He intends to book a first-class compartment on the Orient Express, run by his former friend and colleague, Monsieur Bouc. The train is surprisingly full, but Bouc manages to secure Poirot a spot in the first-class cabin. While aboard the Orient Express, Poirot meets a host of peculiar characters: an aging Russian princess, her Swedish companion, a Hungarian countess, a Minnesota housewife, a Scottish colonel, an English governess, a French conductor, a disagreeable American businessman, and his anxious secretary. While aboard the train, the angry businessman, Samuel Ratchett, corners Poirot and demands Poirot to investigate a series of ominous letters that have been sent to Ratchett, threatening his life.

As a snowdrift halts the Orient Express in its tracks, Ratchett is found stabbed multiple times in his locked train compartment. Poirot is tasked by Monsieur Bouc to solve the murder, as the killer could still be in their midst. As Poirot investigates, conflicting clues and convoluted alibis lead him to dead ends. Over the course of 48 hours, will Poirot be able to solve the case of the Murder on the Orient Express?