Set in Old California in the wake of the Mexican-American War, Ramona is two stories at once. It is the story of the love between a part-Native American orphan girl, Ramona, and Alessandro, a young Indian sheepherder. It is also the story of racial prejudice and the clash between cultures as California changes from a Spanish colony to an American territory. Ramona is the ward of Señora Gonzaga Moreno, who despises the girl for her race but honors the dying wish of the Señora's sister, Ramona's foster-mother, to raise her as her own. Señora Moreno embodies the aloof arrogance of Spanish nobility, hating both the Americans who dispute her claim to her vast rancho, and the Indians, whom she places in the same social class with slaves. Her only semblance of love is reserved for her son Felipe.

Despite the Señora's machinations, Ramona and Alessandro fall in love, and eventually elope. But their life together is not an easy one, as they roam the Southern California searching for a home. Their many hardships cannot dull their love for one another, but they soon take a toll that changes their lives forever. (Introduction by Christine Dufour)