A nurse, Minerva Halliday, is heading north on the Orient Express from Venice to Paris to Calais. She notices an elderly patient walking down the car and observes that he's seriously ill. She confirms the man is going to Calais and on to London. Minerva goes over and simply says "I believe" to him and then walks away.
Later, the conductor asks for a doctor and Minerva realizes the man is sick. She offers her services and checks on the man, and determines he's seemingly dead. Minerva orders the conductor out and confirms her diagnosis, and then tells him that she knows who he is and what is the cause of his illness: a disease of people. The passenger groans and then looks up to agree, and wonders how she knows. Minerva explains that when she was six, she met someone like him in Ireland at her uncle's house in the country. A shadow came to her room and whispered to her. Minerva explains that he's already a ghost and he laughs in agreement.
A priest comes in to administer the last rites and is surprised to find the passenger dead. Minerva ushers him out and offers her help to the passenger. He explains he's going to a castle in England where he can hide forever. Minerva warns that it's impossible without her and offers to help him across the English Channel. When he wonders why she would help, Minerva insists that she knows him from the moors of England, and she believes. The passenger explains he lived near Vienna for two hundred years, but the growing disbelief caused him and his others to flee north. He no longer knows who he is given how the rain has erased his name from his gravestone. Minerva explains that she is something of a ghost herself and will lend her belief to him, and it will be a lark.
They arrive in Paris and the passenger worries that the disbelief of the crowds will dispel him. Minerva takes him to a cemetery of the famous and they find the grave of one who was a believer. They find the headstone of Chopin and as the passenger listens, Minerva secretly weakens and takes a pill.
Afterward, they continue north to Calais where partygoers weaken the passenger. Minerva offers him the works of Doyle, Poe, and Hamlet to read and reinforce. He recites Hamlet to the pleasure of Minerva and the passengers.
At Calais, they board a ship and the passenger worries there is nowhere to hide. Minerva insists that he trust her and they are surrounded by children. She offers to have the passenger tell them a ghost story and makes sure that they all believe. The passenger gathers them around and then levitates into the air and confirms they believe. The nuns call the children away before he can continue, but their belief is enough.
The passenger and Minerva board the ship and he insists that he's doing much better. As he strides confidently aboard, in much better form, Minerva collapses as her heart gives out. She glows with light and the police call an ambulance. The passenger returns and the ghost of Minerva comes to him. He thanks her for her intentions and she says that she has nowhere else to go and will accompany him on his remaining journey. As the ship departs, Minerva admits she didn't know who she really was. He welcomes her on his journey and they embrace for a moment before departing.