The English Patient follows the stories of four key characters, whose lives are entwined near the end of WWII, in the Italian Villa San Girolamo. Hannah is a young, war-damaged nurse. She takes care of the titular English patient, an enigmatic man with terrible burns, who slowly reveals his involvement in the desert explorations of the 1930s, and his affair with Katherine Clifton, a young English woman. Hannah and the English patient are joined at the villa by Carravaggio, a thief, and Kip, an Indian sapper with the British Army, who comes to love Hannah whilst struggling with his own past.

Ondaatje draws the strings of the four stories together, as the central identity of 'the English patient' is revealed.