The Narrow Road to the Deep North spans decades of the life of Dorrigo Evans and the people he encounters over the course of his adult life. Dorrigo becomes engaged to a very correct young woman named Ella Lansburg one evening, without really intending to make the proposal. He falls in love with a young woman named Amy who Dorrigo later learns is married to his uncle, Keith Mulvaney. Amy and Dorrigo begin an affair though Dorrigo is already in the military and is expecting to be moved out at any time.

Dorrigo is in active duty only a short time when he is captured and held as a Prisoner of War. The POW camp is manned by Japanese and Korean soldiers. The situation is horrific with starvation and deprivation a daily occurrence. Dorrigo, a surgeon, becomes the commanding officer among the POWs and feels a personal responsibility for the well-being of all the prisoners. He feels the loss of each death and is often forced into situations of compromise. When the guards are brutally beating a man named Darky Gardiner, Dorrigo tries to intervene. When a Japanese commander offers Dorrigo quinine that might be used to save the lives of other men, Dorrigo accepts the offer, knowing he is trading the life of one man for the medicine. He later learns that Darky Gardiner is actually his biological nephew.

During his time as a POW, Dorrigo learns that the pub owned by Amy and her husband exploded and Dorrigo's fiance, Ella, tells him that Amy's remains were identified among the victims. She actually isn't dead but Dorrigo doesn't know this for decades. Dorrigo and Ella marry upon his return after the war. They have three children and settle into an uneasy relationship, though Dorrigo hates himself for never being able to fully love Ella and his children. Dorrigo becomes a renowned surgeon and a known speaker among POW gatherings. He spends years in illicit affairs and seeking a way to feel alive, but never achieves it. He is fatally injured as an old man when a car driven by a drunk teen crashes into his Bentley.

Meanwhile, other people who met Dorrigo along the way go on with their lives. Jimmy Bigelow, the man who'd been the trumpeter at many funerals in the POW camp, lives to be more than ninety and forgets the atrocities of the camp by the time of his death. Ella reconciles herself to the marriage with Dorrigo, who is never faithful and never returns her love. Amy develops cancer and lives out the last days of her life peacefully, with her sister's family.

Several of the Japanese and Korean soldiers are killed as war criminals. The commander of the POW camp, a Japanese man named Nakamura, discovers that his name is listed among the men being sought for war crimes. He goes into hiding for some years until comes to realize that the hunt is no longer active. He then marries and has a family, and spends most of his life trying to reconcile himself with his crimes, which he sees as merely doing his duty. He tries to lead a good life as a kind man but sometimes believes the dictates that ruled his life as a soldier were all lies.