The story opens with an unseen hand painting a swimming human figure. As the illustration is finished, the background shifts to a desert landscape and the figure blends in with the dunes.

A biplane is flying across Northern Africa. In the front seat is a woman who appears to be asleep. The plane is spotted by a military outpost. The soldiers begin yelling in German and open fire on the plane with a flak cannon. The plane is severely damaged. The pilot attempts to pull the woman from the front of the plane but it soon bursts into flame and the man is forced to bail out. His face, arms and chest take the full force of the fire. The man is later found by a small group of Bedouins, who transport him to a camp where a healer mixes a salve from a series of small vials and applies it to the horrific burns on the pilot's face.

At a seaside resort in Tuscany in 1944, a British officer is interrogating the same man, whose face and hands have mostly healed but have left him weak, scarred and in need of regular morphine injections to stifle the pain. The pilot is being tended to by a young nurse named Hana. The man admits to being able to speak both English and German and that he can't remember anything before his accident. Finding it very difficult to breathe, he asks the British officer to let him rest.

Hana is later seen in a camp near a battle zone in Tuscany donating blood. A nearby patient, who is close to death, asks if there's anyone in the tent from his Canadian home town. Hana's friend Jenny mentions that Hana's fiancé is from the same town. The dying soldier says that he was killed a couple of days ago. Hans becomes distraught; she believes she's cursed and that anyone who tries to be close to her dies.

The medical unit packs up and heads north through Italy, following the Allied front as they push the German army back into Europe. As the caravan drives along a gravel road, Jenny comes alongside Hana's truck in a jeep, asking Hana for money to spend in the next village. Hana laughingly refuses but still gives Jenny some money. As her jeep zips away it hits a mine and explodes. While a couple of men sweep the road with metal detectors Hana suddenly walks past them toward Jenny's jeep. The mine crew yells for her to stop, telling her she could step on another mine. Hana has spotted a small bracelet belonging to Jenny in the road -- one of them men carefully picks it up and gives it to her. The other man, a Sikh in a turban, goes back to disarming a mine he'd found.

Hana decides that she'll take the burned man to a abandoned villa on a nearby hilltop and tend to him until he dies. Her commanding officer is reluctant but also realizes she can use some time off from the front line. He tells her to rejoin the unit in Livorno after the burned man dies.

Hana sets about making the bombed-out villa livable and has her patient settled into one of the bedrooms. A stranger shows up, David Caravaggio, whom is missing both thumbs. He claims to be working for the Italian government, disarming local citizens and partisans before they can cause trouble behind the front. Caravaggio brings her some eggs and slyly steals a few vials of morphine that Hana has for the patient.

The man in the turban, Kip, also shows up when Hana plays Bach on an old piano. He fires a single pistol shot to stop her so he can inspect the piano, saying that the Germans would place bombs in pianos to kill civilians. Surely enough, he finds one. He says he'll stay with his junior officer, Hardy, and inspect the rest of the house and property for more explosives. Hana jokes with Kip about how her mother always said she'd summon the man she'd marry by playing the piano.

The burned patient remembers the time before the outbreak of the war, despite his claim that he has amnesia. Then known as Count Laszlo de Almásy, a cultured and introverted Hungarian cartographer, he was part of an expedition to map the Sahara Desert from the air. Almásy's best friend is Madox, who helps bring in a couple of wealthy benefactors to fund their efforts. The donors are Geoffrey and Katherine Clifton who have also brought another plane that will help expand their expedition. Almásy is leery of Katharine joining them in the desert, but is also very attracted to her. He meets her one day in the Cairo bazaar after she's bought a woven table covering. He insists they take it back to the merchant she bought it from, saying she'd been cheated because she didn't bargain with the man, something the merchants find insulting. She insists they don't bother.

Geoffrey flies off to Cairo on business, leaving Katherine behind. The group inspects a remote area where Almásy discovers a hill in the shape of a woman's back, a legend he'd been informed of by an old Bedouin. Nearby he finds a cave filled with ancient drawings of people swimming. The team spends a few days documenting and exploring the cave while Katherine takes the opportunity to paint watercolor illustrations of the swimmers. She offers to paste them into Almásy's worn copy of Herodotus' Histories but he politely refuses, saying the paintings are "too good." She walks away insulted however Almásy is fearful of becoming too close to her.

While driving back to Cairo, one of their trucks tumbles down a sand ridge and overturns. Several of the party, including Madox and a couple of injured members, agree to drive back to Cairo for help. Katherine stays behind so as not to weigh down the convoy. That night everyone is forced to take refuge in the trucks while a sandstorm rages. Katherine and Almásy talk about various types of desert storms. Almásy lightly strokes her hair; Katherine doesn't resist. The two fall asleep and miss Madox' return. They then dig out the 2nd truck and begin to dig up supplies that were scattered in the wreck. Katherine tucks a few of her small watercolor paintings into Almásy's copy of Herodotus' Histories. They are interrupted by Madox, who'd set off a flare because he was lost.

Back in Cairo, Katharine visits Almásy at his hotel room and the two begin a torrid love affair. In the bath together, they talk about what they missed while in the desert and seem happy until Almásy tells her that she should go back to Geoffrey. Katharine becomes upset and leaves in anger. However, their attraction to each other is too passionate and they continue the affair. At a lavish dinner party that marks the end of their expedition due to the outbreak of World War II and halt to their funding, Almásy arrives late and drunk. He regales the group with an explanation of the censored lyrics to Irving Berlin's "Cheek to Cheek". Though he makes an embarrassment of himself, he calms down and joins the group for dinner. Later he dances with Katharine but their time together is awkward. Geoffrey takes notice of odd behavior in his wife and suspects she may be involved with Almásy.

At the villa, Caravaggio confronts Hana, asking some pointed questions about her patient. She mostly refuses, suspicious of his motivations. Caravaggio has his own history, connected to Almásy: he was an important figure working for the Allies before the Nazi campaign in Northern Africa and was hunted by the Germans. While the city of Cairo is invaded by the German navy and Luftwaffe, one of Caravaggio's commanding officers rants about how the Germans were able to make a lightning strike on Cairo using the very maps that Almásy, Madox and the Cliftons had drawn. While standing in a crowd of people being documented by the Germans, Caravaggio tried to leave his line and was captured. He was interrogated for an indeterminate period of time, chained in a small room. A German officer, Mueller, knew that Caravaggio was an Allied spy who operated under the alias "Moose". Demanding he give up the names of his comrades, Mueller cruelly has a Muslim nurse cut off Moose's thumbs with a straight razor. Moose vowed revenge against both Mueller and the man who'd given a picture of him to the Germans. After finding and killing Mueller, believing also that Almásy is the man he's been looking for. Hearing from one of Hana's friends that she was tending to a patient who carried a copy of Herodotus' Histories and was an expert on popular songs, he set out to find her.

A romantic relationship begins to develop between Hana and Kip. One evening he takes her into the nearby town of Siena to see the frescoes in the town's cathedral. Kip has arranged a rope and pulley system to lift Hana off the floor to see them up close. Hana is grateful for such a romantic gesture and she and Kip spend an intimate night in the villa's barn. Hardy comes looking for Kip the next morning, saying a large bomb had been found under a nearby bridge. Hana looks very worried, thinking the curse that haunts her will kill Kip. While Kip tries to disarm the bomb, a convoy of Allied tanks and other vehicles roar across the bridge. Kip remains very cool and is able to disarm the bomb, collapsing in relief upon it.

The raucous convoy had been celebrating big news: the war in Europe is over. The whole town erupts in in joy, with a group led by Hardy climbing a bronze statue in the main square. Back at the villa, Hana, Caravaggio and Kip are all dancing happily when they see a flash in town and hear an explosion. Kip races to the scene and finds the statue Hardy had been climbing and his friend bloodied and dead. A junior officer explains they were drunk and goofing around when Hardy climbed the statue and a bomb went off. Kip locks himself in the barn for a long period, mourning the loss of his friend. When he finally comes out, he talks to Hana about his friend, about how they were friends but never really spoke of anything too personal. He still wishes to continue his relationship with Hana and will find her when things have calmed down.

Almásy relates the final part of his story before his injury to Caravaggio when the latter accuses him of killing Geoffrey and Katharine. Back in the desert, Almásy is finishing the job of packing up the group's base camp near the Cave of Swimmers. Geoffrey had volunteered to fly out and pick him up but on his approach he flies in too fast, seemingly aiming for Almásy. The plane crashes, narrowly missing Almásy. When Almásy reaches the wreck, he finds Geoffrey dead and Katharine in the front seat, badly injured. She tells him that Geoffrey was ranting during the last seconds of their flight, saying he loved her. As Almásy carries her to the cave, she finally admits her love for him and he cries. In the cave, he builds her a fire and binds her broken ankle. He also tells her she has a few broken ribs making it difficult to breathe. He leaves her with a small lantern, his copy of Herodotus and a few pencils. He tells her he'll hike through the desert to find help. He spends three days walking and finally arrives at a British army outpost. Desperate to return to the Cave of Swimmers, he rants about Katharine dying out in the desert, begging the British soldiers to give him a jeep. When he becomes angry and grabs one of them, another hits him, knocking him out. He wakes up shackled in the back of a jeep with the guards claiming, due to his unusual accent, that he might be a German spy. On a train to the Mediterranean coast, he asks if he can use the toilet. He tricks the guard into thinking the door to the toilet is locked and attacks the man, killing him and unlocking himself. He jumps from the train and limps off. He finds the German army in the desert, who happen to have taken possession of Madox' plane. Giving them the maps he and his team had produced, Almásy is able to acquire the plane and enough fuel to rescue Katharine. However, Katharine has already died alone in the cave, having written a last letter to Almásy. He flies out with her body, returning to the opening scene of the story where his plane is shot down by the Germans. Hana visits Almásy one last time in the villa, preparing to give him his morphine. As she prepares another syringe, he weakly pushes the remaining vials to her, silently asking her to inject them all so he'll die. She weeps but does so, a peaceful smile crossing his face. When she joins a small group heading out of the area in a truck, she smiles to herself.