This story begins just before the outbreak of the Second World War. A group of mapmakers are working in the desert in Egypt. Among their number are Geoffrey Clifton, his wife Katharine, Madox, and Count Almasy. The Cliftons have only been married for a year, but they have known each other since they were children. When Katharine joins the group at their camp in the desert, Count Almasy is not at all friendly to her. She is the only woman in the group, and she is very beautiful. Almasy is obviously attracted to her, and finds it difficult to relax with her near him. Geoffrey Clifton is in fact working as a spy for the British, and has to return to Cairo. While he is away, Almasy and Katharine are alone together. They have to spend a night together in their jeep because of a sandstorm. Slowly they begin to warm to each other.
The group goes to Cairo to join Clifton. Almasy follows Katharine in the market, but she tells him to leave her alone. Shortly afterwards she visits him in his flat and their love affair begins in earnest. At a Christmas party where Katharine is helping to serve the food and tea, Almasy appears, desperate to meet her. They make love only a short distance away from where all the guests are enjoying their Christmas meal, and are almost caught in the act by Clifton who is dressed up as Santa Claus.
On the afternoon of the Cliftons' first wedding anniversary, Clifton rings Katharine to say he is busy at his office and won't be home till late. He wants to surprise her, and drives to their home with a bottle of champagne. As he arrives, he sees his wife getting into a taxi. He waits for her to return, but it is a long wait. Katharine spends the night with Almasy.
Before long Katharine decides to end her relationship with Almasy. She loves her husband and doesn't like deceiving him. Almasy is furious, and tries to make her come back to him. This only makes the situation worse. Everyone in the group is aware of their relationship, and in fact Katharine still loves Almasy.
The war begins and they are told they must leave Egypt at once. Almasy goes back to their camp in the desert to pack their belongings away. Clifton arrives in his aeroplane to collect him, but as he comes in to land, he crashes the plane on purpose in an attempt to kill Almasy. Almasy is able to escape injury, but Clifton dies in the crash, and Katharine is badly injured. Her ankle is broken and she cannot walk. Almasy carries her into a cave and tells her to wait while he goes to get help. She is afraid of dying in the desert on her own, and makes him promise he will come back for her.
Almasy walks for three days to the nearest town. When he arrives, he is tired and thirsty, and very worried about Katharine. The British soldiers in the town ask him who he is and what he wants. When he tells them his name, they think he is a German and arrest him. They put handcuffs on him and put him on a train. He manages to escape, but by now he is further from the cave and Katharine than ever. He knows that if he doesn't get back to her soon, she will die. In desperation he seeks the help of the Germans. He gives them information about the desert and Cairo, and in exchange they give him fuel for Madox's plane. He flies to the cave, but he is too late. Katharine is already dead.
He puts her dead body into the plane and takes off. While the plane is flying over the desert, it gets shot down by the Germans. Almasy manages to escape from the burning plane, but he is very badly burned. He is found by some passing Arabs who look after him and take him to a British hospital. There he recovers enough to speak, but he says he cannot remember who he is. The doctors and nurses call him 'the English patient.'
As the war draws to a close, Almasy is taken to Italy, where a nurse called Hana looks after him day and night in a former monastery. They are joined by a Canadian man wearing mittens on his hands. He is David Caravaggio, a spy who was arrested by the Germans who cut off his thumbs. Caravaggio thinks that the badly burned man being looked after by Hana is the man who betrayed him to the Nazis. Caravaggio confronts Almasy, and tells him he knows who he is. However when he hears the sad story of Almasy and Katharine's love, Caravaggio is so moved, he loses all desire for revenge.
Soon another visitor comes to the monastery. He is an Indian called Kip, who is working for the British as an expert in clearing the mines left by the Germans. Hana falls in love with Kip after he shows her the beautiful paintings on the walls of an Italian church.
One night there is a storm, and they carry the sick Almasy out into the garden so he can feel the cool freshness of the rain on his face. It is the last happiness he will enjoy. Every day his lungs are growing weaker and weaker. When he jumped from his burning plane, he breathed in much smoke. His lungs were irreparably damaged. As the war ends, so does the life of the English patient, the Hungarian Count Almasy.