An interwar vintage British biplane, flying across a sea of desert, is shot down by German gunners. The badly burned pilot is pulled from the wreckage and rescued by a group of Bedouin.
Hana, a French-Canadian combat nurse of the Royal Canadian Army Medical Corps during WWII, learns from a wounded soldier that her boyfriend has been killed in action.
In October 1944 Italy, Hana is caring for a dying, scarred-from-burns English-accented patient who says he cannot remember his name. His only possession is a copy of Herodotus' Histories, with personal notes, pictures, and mementos stored inside. When a nurse friend is killed in front of her, Hana decides she is a curse to those who love her. She gains permission to settle in a bombed-out monastery with her patient, as he suffers during relocations of her hospital unit.
They are soon joined by Lt. Kip, a Sikh sapper in the British Indian Army posted with Sgt. Hardy to clear German mines and booby traps. David Caravaggio, a Canadian Intelligence Corps operative who was tortured during a German interrogation, also arrives at the monastery. Caravaggio questions the patient, who gradually reveals his past through a series of flashbacks. Over the days of the patient relating his story, Hana and Kip begin a shy love affair.
The patient reveals that in the late 1930s, he was exploring a region of the Sahara. He is, in fact, Hungarian cartographer László Almásy, who was part of a Royal Geographical Society archeological and surveying expedition with a group including his good friend, Englishman Peter Madox, and British couple Geoffrey and Katharine Clifton, who own a plane and contribute with aerial surveys.
Almásy learns information from a Bedouin which helps the group discover the Cave of Swimmers, an ancient site of cave paintings. The group begins to document their find, during which time Almásy and Katharine fall in love. He writes about her in notes folded into his book, which Katharine discovers when Almásy awkwardly accepts her offer of two watercolours she has painted of the cave imagery and asks her to paste them into the book.
The two begin an affair on their return to Cairo, while the group arranges for more detailed archaeological surveys of the cave and the surrounding area. Almásy buys her a silver thimble as a gift. Some months later, Katharine abruptly ends their affair from fear Geoffrey will discover it. Shortly afterward the archaeological projects are halted due to the onset of the war. Madox leaves his Tiger Moth airplane at Kufra Oasis before his intended return to Britain.
Caravaggio reveals that he has been seeking revenge for his injuries, and has killed the German interrogator who cut off his thumbs and the spy who identified him, but has been searching for the man who provided maps to the Germans, allowing them to infiltrate Cairo. He suspects the patient is Almásy, asking "Did you kill the Cliftons?", to which Almásy concedes "Maybe... I did".
Reminiscing for Caravaggio, with Hana listening in from an adjoining room, Almásy recalls packing camp in 1941 when Geoffrey arrives overhead. He dives straight for Almásy, who jumps out of the way. Scrambling over to the wreckage, he finds Geoffrey dead at the controls and Katharine badly injured in the front seat. She tells him Geoffrey knew, and was attempting a double murder-suicide. Almásy carries her to the Cave of Swimmers. He notices she is wearing a chain bearing his gift, and she declares she has always loved him.
Leaving her in the cave with provisions and his book, Almásy walks three days cross-desert. Arriving at British-held El Tag, he explains the desperate situation and asks for help, but a young officer detains Almásy on suspicion of being a spy. Transported away by train, Almásy escapes and eventually comes into contact with a German army unit. They take him to the Kufra Oasis, where Madox has hidden his plane. Exchanging maps for fuel, Almásy takes to the air and finally reaches the cave, where he confirms that Katharine has died. He carries her body to the plane, and he is burned when shot down, connecting to the start of the film. After hearing the story, Caravaggio gives up his quest for revenge.
Kip is reposted once he has cleared the area of explosives; he and Hana agree they will meet again. Later, pushing several vials of morphine toward Hana, Almásy tells her he has had enough. Though visibly upset, she grants his wish and administers a lethal dose. As he drifts to sleep, she reads him Katharine's final letter, written to Almásy while she was alone in the cave. The next morning Caravaggio returns with a friend, and they get a lift to Florence. Hana holds Almásy's book tightly as they ride away.
