Japanese-Americans have been part of United States' history for centuries. Early 20th century Japanese immigrants to the United States, the Issei, are important contributors to American life and built communities across the country, particularly in San Francisco. Their children, the Nisei or second-generation Japanese Americans grow up conceiving of themselves primarily as Americans, speaking English as their first language and seeking to fully merge into American culture. This is the nature of Japanese American life in the 1930s where Desert Exile begins its story.

The author, Yoshiko Uchida, and her family live in San Francisco. Her father, Dwight, and her mother, Iku are Issei immigrants, both of whom becomes familiar with American culture in Kyoto and are chosen as each other's spouses by American professors at Doshisha University in Japan. Dwight and Iku are both Christians and spend much of their lives as devout members of their local church. Yoshiko and her older sister Keiko are raised in a happy home. Their family is fairly well-to-do and Yoshiko's parents do not discourage her or Keiko from integrating.

The primary event of Desert Exile is the internment of Japanese Americans by the United States government during World War II. Within weeks of the bombing of Pearl Harbor, thousands of Japanese Americans, many of whom are United States citizens, are rounded up and sent to concentration camps across the United States. While many accounts of internment have been recorded, Yoshiko gives her account in Desert Exile in order to communicate her own experience of oppression during World War II and to contribute one more perspective to teach Americans to safeguard their rights so that such mistreatment never happens again.

Desert Exile is short, composed of eight chapters and an epilogue, most of which concern internment. Chapter 1, The House on Grove Street, introduces the Uchida family and explains their origin, community, personalities, occupations and interests. Chapter 2, On Being Japanese and American, introduces an important theme of the book—the Nisei's divided identity between being Japanese and American, and their feeling of a lack of identity, since many do not know Japanese but are not accepted by white America. It also discusses the relationship between the Issei and the Nisei.

Chapter 3, Pearl Harbor, begins with the attack on Pearl Harbor and their hurried and irrational reaction of the United States' government and many American citizens to Japanese Americans, questioning their loyalty to the United States and treating them as a fifth column. Chapter 4, Evacuation, covers the evacuation of the Uchida family after Dwight has been taken away. The Uchida women have to pack up their things before being shipped off by the American government.

Chapters 5 and 6, A Horse Stall for Four and City behind Barbed Wire covers the Uchida family's stay at the Tanforan concentration camp and Chapters 7 and 8, Topaz: City of Dust and Topaz: Winter's Despair, cover their transfer to Topaz in Utah and their eventual release. The Epilogue looks back on Yoshiko's experiences, discusses what has happened to the Uchida family since being released and explains Yoshiko's rationale for writing the book.