The Great Fire is the tale of Major Aldred Leith, a decorated war hero. The story begins in Asia in 1947 and encompasses two years, crosses several continents, and concludes in the remote island nation of New Zealand. Aldred is the son of a famous author, and has hopes of being an author himself; as the novel opens, he is exploring the war-ravaged lands of Asia for a book he is writing. His book will be the summation of his experiences and explorations of Asia, the land and its peoples, in the aftermath of World War II. At this point, Aldred has already spent a year traversing China for research and is now on his way to Japan, with plans to continue his work from the hills of Kure. Early on in the story, it becomes clear that Aldred has been affected both by the tragedies of war, and by what he remembers as a loveless childhood; his experiences have led him to harbor a deep cynicism for his fellow man.

Once in Japan, Aldred meets Benedict and Helen Driscoll, siblings. Benedict is a young man of twenty, but he suffers a debilitating disease from which will eventually rob him of the capacity for speech and mobility; he is dying, and the sixteen year old Helen is Benedict's primary care giver and companion.. Aldred develops an immediate attraction for Helen upon his arrival in Kure, though at thirty-two, he struggles with the improbability of a relationship with the teenaged girl. Benedict and Helen Driscoll provide the backdrop against which the reader will learn of Aldred's war-torn Asia. As his relationship with the Driscoll siblings begins to develop, Aldred also comes to experience the death of his cynicism, the rebirth of his optimism, and his own capacity for love.

In the midst of his time with the Driscolls, Aldred hears from his old friend, Peter Exley. Peter is a member of the British Army and has come to China to prosecute war criminals. China has just come out of the Second World War, only to find itself on the verge of its own Civil War. Hong Kong is dismal, and clean water and food are in short supply. The author uses the interactions between Peter and his fellow soldiers and coworkers to demonstrate the differences in people's abilities to adapt in this postwar society. Peter's own attempts to adapt revolve around his desire to settle down and start a family; his awareness of others is often influenced by his perceptions of whether or not they would be viable companions in that goal.

Peter invites Aldred to visit Hong Kong. Aldred accepts the invitation and the opportunity to put temporary distance between himself and Helen, since he believes a relationship with the young girl would be impossible. When Aldred arrives in Hong Kong, Peter manages to convince his friend that he is happy there. During his visit, Aldred meets Audrey Fellowes, who is in Hong Kong visiting her relatives. Aldred speculates that Audrey and Peter could have a relationship if he arranged for them to meet. Meanwhile, in Aldred's absence, Thaddeus 'Tad' Hill is introduced to Helen Driscoll. Tad is interested in pursuing a relationship with Helen but realizes that her feelings are for someone else. Aldred finally accepts the convictions of his feelings for Helen and returns to Kure knowing he is determined to have her.

Aldred and Helen grow closer, though since Aldred believes that Helen's parents would not consent to his attentions to Helen, the relationship is kept secret from them. As their relationship grows, however, Benedict's condition worsens. He becomes physically incapacitated, and Helen and Aldred become his only sources of exposure to the outside world. Aldred continues in his research during this time, and one day returns from short trip exploring Nagasaki to find Helen distraught. Her parents had sent her on a false errand and moved Benedict to a Tokyo hospital in her absence. Ultimately, Benedict will be moved all the way to California, in the United States, for care. Helen will not see her brother alive again.

Aldred gathers the mail that had collected while he was in Nagasaki and immediately travels to Tokyo to check on Benedict. In the course of his errand, he receives report after report of bad news. He runs into Audrey Fellowes at the hospital, and is informed that Peter has contracted a serious illness and been admitted to a hospital in China. In his mail, Aldred discovers that he had received word of his father's death. Returning to Kure with news of Benedict, Aldred learns that General Driscoll has received a post in New Zealand and that Helen and her parents will immediately be moving to that remote island nation. Faced with the need to return home to London to settle his father's estate, Aldred is unable to remain with Benedict or travel to see Peter. He requests permission for Helen to become a ward of his mother's until she is of an age to marry, but his suit is denied by the elder Driscolls. Without her parents' approval, Aldred is unable to confirm his relationship to Helen, and she moves to New Zealand with her parents.

Aldred returns to London to settle his father's estate. It is here that Aldred resolves his conflicted relationship with his mother, Iris. He also becomes reacquainted with Aurora Searle, a friend and former romantic liaison who had been the mistress of Aldred's father for a number of years. It is while Aldred is in London, and Helen in New Zealand, that word of Benedict's death comes. Helen's parents board a ship to America to claim his body, and Aldred travels to New Zealand to join Helen, who has remained behind.