In The English Patient, the past and the present are continually intertwined. The narrative structure intersperses descriptions of present action with thoughts and conversations that offer glimpses of past events and occurrences. Though there is no single narrator, the story is alternatively seen from the point of view of each of the main characters.

The novel opens with Hana, a young nurse, gardening outside a villa in Italy in 1945. The European theater of the war has just ended with the Germans retreating up the Italian countryside. As the Germans retreated, they left hidden bombs and mines everywhere, so the landscape is particularly dangerous. Although the other nurses and patients have left the villa to escape to a safer place, Hana decides to stay in the villa with her patient.

Hana does not know much about the man for whom she cares. Found in the wreckage of a plane crash, he been burned beyond recognition, his whole body black and even the slightest touch painful to him. He talks about the Bedouin tribe who found him in the wreckage, cared for his wounds, and eventually returned him to a British camp in 1944. He does not know who they were, but he feels grateful to them nonetheless. To pass the time, Hana reads to the English patient—she assumes he is English by his manner and speech—and also gardens, fixes up the villa, and plays hopscotch. Sometimes she picks up the patient's notebook, a copy of Herodotus's The Histories marked throughout with his own notes, figures, and observations, and reads to him or to herself.

One day, a man with bandaged hands named Caravaggio arrives at the villa. He is an old family friend of Hana's father, Patrick, and had heard about her location while he was recovering in a hospital a few miles away. In Canada, where Caravaggio knew Hana years ago, he was a thief. He tells her how his skills were legitimized in the war and how he put them to use working for British Intelligence in North Africa. He tells her that the Germans caught him after an attempt to steal a camera from a woman's room. They tortured him and cut off his thumbs, leaving his hands mutilated and nearly useless. Although he has recovered somewhat, he is still addicted to morphine. In the villa, he reminisces with Hana and mourns with her over the death of her father in the war.

As Hana plays the piano in the library, two soldiers come in and stand alongside while she plays. One of them is Kip, an Indian Sikh trained as a sapper, or bomb-defuser, in the British army. After hearing the piano, Kip has come to clear the villa of bombs, knowing that the Germans frequently booby-trapped musical instruments. Kip and the English patient get along very well, as they are both experts in guns and bombs and enjoy talking to each other and sharing stories. Kip makes camp in the garden of the villa and becomes a part of the "family" that now exists there. He goes off into town every day to clear more bombs from the area and to bury fellow sappers who have died. Kip's job is extremely dangerous. He feels a strong attraction to Hana, and soon they become lovers.

Asked about his past, the English patient begins to tell the others his story. His real name is Almasy, though this is not definitively confirmed until Chapter IX. He spent the years from 1930 to the start of World War II exploring the North African desert. His job was to make observations, draw maps, and search for ancient oases in the sands. Along with his fellow European counterparts, Almasy knew every inch of the desert and made many trips across it. In 1936, a young man from Oxford, Geoffrey Clifton, and his new wife Katharine, joined their party. Geoffrey owned a plane, which the party found especially useful in helping to map the desert. The explorers, Almasy, and the Cliftons got along very well. One night, after hearing Katharine read a passage from his book of Herodotus, Almasy realized he was in love with her. They soon began a torrid and tumultuous affair. Everywhere they stole glances and moments, and they were obsessed with each other. Finally, in 1938, Katharine broke off their affair, telling Almasy that Geoffrey would go mad if he ever found out. Although their affair was over, Almasy remained haunted by her, and he tried to punish her for hurting him by being particularly mean to her in public. At some point, Geoffrey somehow found out about the affair.

World War II broke out in 1939, and Almasy decided to close up their camp and arranged for Geoffrey to pick him up in the desert. Geoffrey arrived in his plane with Katharine. Geoffrey attempted to kill all three of them by crashing the plane into Almasy, who was standing on the ground. The plane missed Almasy, but the crash killed Geoffrey, left Katharine severely injured, and left them with no way to escape the desert. Almasy placed Katharine in a nearby cave, covering her with a parachute for warmth, and promised to come back for her. He walked across the desert for four days until he reached the nearest town, but when he got there, the English army would not help him get back to Katharine. Because Almasy had a foreign-sounding name, the British were suspicious and locked him up as a spy, prevented him from saving Katharine.

Almasy was eventually released, but he knew it was too late to save her. He worked for the Germans, helping their spies make their way across the desert into Cairo. After he left Cairo, his truck broke down in the desert. Without transportation, he walked to the cave to get Katharine. He took her dead body and placed it in a plane that had been buried beneath the sand. The plane malfunctioned during their flight and caught fire. Almasy parachuted down from the plane, his body covered in flames. That was the point at which the Bedouins found him and cared for his burns.

Little by little, the English patient tells this whole story. Caravaggio, who has suspected the English patient was not really English, has his suspicions confirmed. He fills in gaps for the Almasy, telling him that Geoffrey Clifton was really an agent of British Intelligence and that Intelligence had known about Almasy and Katharine's affair the whole time. They knew Almasy had started helping the Germans and planned to kill him in the desert. They lost him between Cairo and the plane crash, and now, of course, he is unrecognizable.

The focus of the novel shifts to Kip, and we are told his entire story. Although Kip's brother always distrusted the west, Kip went willingly to serve in the British army. He was trained as a bomb defuser under Lord Suffolk, a true English gentleman, and was then virtually welcomed into an English family. Kip soon grew quite skillful at his job, able to figure out both the "joke" and the "character" of each bomb he tackled. Lord Suffolk and his group were blown up defusing a bomb, and Kip decided to leave England and become a sapper in Italy.

Kip has felt emotionally removed from everyone in his job as a sapper. When he meets Hana, he uses her to once again connect to humanity. All the residents of the villa celebrate Hana's twenty-first birthday, and Kip grows comfortable as her lover. When August comes, however, Kip hears on the radio of the atomic bomb that the United States has dropped on Japan. He becomes enraged, knowing that a western country would never commit such an atrocity against another white country. He takes his gun and threatens to kill the English patient, whom he sees as a symbol of the West. Kip does not kill Almasy, but takes off on his motorcycle, leaving the villa forever. Years later, he is a doctor in India with a family of his own. Though he is happy and fulfilled in his new life, he often wonders about Hana.