Set on a train journey from Ostend to Istanbul, the book was renamed Orient Express when it was published in the United States.

But though some elements in the novel have been described as "melodramatic incidents that could find a place in the most conventional of thrillers", Greene's aim is to use them to go beyond their basic paradigm in order "to produce work that can be taken as art while also reaching a large audience".

Among the preparations for writing his book, he mentions taking notes on a train journey to Cologne – "you may be sure the allotments outside Bruges were just where I placed them in April, 1931".

He also plotted key scenes in which the characters were to be established through dialogue and he put himself in the mood by daily playing Arthur Honegger's "Pacific 231" on his gramophone at home.

B. Priestley was given a review copy and, coming to the conclusion that Savory was based upon him, threatened a libel suit and also to leave their joint publisher, Heinemann.

[3] The novel focuses on the lives of individuals aboard a luxury express making a three-day journey from Ostend to Istanbul (although Greene uses the old name for the city, Constantinople).

Other scenes in places through which the train passes are also described, as well as Carleton Myatt's high-speed journey by car through the snow-laden countryside to and from the railway station at Subotica.

A major part of the plot focuses on Myatt, a shrewd and practical businessman who trades in currants and has business interests in Istanbul.

Dr. Czinner is an escaped communist leader and former physician, travelling on a forged British passport after five years teaching in an English boys' school.

The three prisoners are kept in a waiting room, but when they realise that Myatt has returned in a car, the resourceful Grünlich breaks open the door and all three make a run for it.

After the train arrives at Istanbul, Myatt discovers that Janet Pardoe is the niece of Stein, a rival businessman and potential business partner.

Despite his own brief encounter with Coral, Myatt now considers marrying Janet and confirming the contract, signed by Eckman, to take over Stein's currant business.

"[4] The epigraph given the book is from George Santayana, "Everything is lyrical in its ideal essence; tragic in its fate and comic in its existence", which indicates its ambivalence of mood.