In 1942, Nazi Germany pursues a plan to pull neutral Turkey into the war by staging an assassination attempt on Franz Von Papen, Curt Furburg, the Turkish ambassador. Colonel Robinson, Sydney Greenstreet, grows frustrated as Von Papen survives and the Russians that the plot’s provocateur was meant to frame have airtight alibis, forcing a pivot to another scheme designed to inflame Turkey’s traditional rivalry with Russia.
An American machinery salesman named Joe Barton, George Raft, climbs aboard the Baghdad–Istanbul Express and is drawn to another passenger, Ana Remzi, Osa Massen. Worried about customs searches once they reach the Turkish border, Ana asks Joe to hold onto an envelope containing securities, the last remnant of her inheritance. Joe agrees, and when he later examines the envelope he finds maps of Turkey with handwritten annotations, clues that hint at something larger than a simple possession.
When the train stops in Ankara, Joe goes to Ana’s hotel to return the property, only to discover that she has been fatally wounded. He watches unseen as Soviet spy Nikolai Zaleshoff, Peter Lorre, searches the dead woman’s luggage, then exits through a window. He is spotted by Tamara Zaleshoff, Brenda Marshall, Nikolai’s sister and partner in espionage.
Turkish policemen take Joe in for questioning, but they prove to be German agents. They haul him to their leader, Colonel Robinson, who wants the maps. Joe refuses to cooperate and is handed over to Mailler, Kurt Katch, who presses for information. Before the Germans can get far, Joe is rescued by Nikolai. The Zaleshoffs reveal that they are Soviet agents, and Joe agrees to fetch them the documents, though his hotel room is soon found ransacked and the papers disappear.
Back at his base, Joe learns that his boss, McNamara, Willard Robertson, has assigned him an assistant, Hassan, Turhan Bey, and the pair head for Istanbul. There, Robinson has bribed a newspaper publisher to run a story claiming that the documents reveal secret Russian plans to invade Turkey. Joe storms in alone and forces the Nazi ringleader at gunpoint to burn the maps. Robinson is handed over to Turkish police and then to his superior, who is deeply displeased and watches him depart by airplane, certain that he has failed. With the critical maps destroyed, Joe and Tamara set their sights on their next assignment in Cairo.