Ramona, by Helen Hunt Jackson, is the story of a young girl who is half white and half Native American, and she is taken into the care of Senora Moreno, the wealthy owner of a sheep ranch, at the request of her foster mother, who passed away. Senora Moreno is a Spanish woman who gives Ramona every material comfort, but who looks down on her for being of mixed race and is never able to love her or truly accept her as her own.

Eventually, Ramona falls in love with Alessandro, a Native American man who comes to work for Senora Moreno during the sheep shearing. Ramona falls in love with him and leaves with him, against Senora Moreno’s wishes. The two marry, and Ramona returns with Alessandro to his village in Temecula. When they arrive, however, they find that the whites have invaded the village. Then, the couple struggles through a series of hardships as the Europeans settle California and attempt to displace the Native American people. Ramona and Alessandro travel from village to village, but they are continually forced from their homes. During their attempts to find refuge, they suffer the loss of a child and the mental breakdown of Alessandro. Later, after Alessandro dies, Senora Moreno’s son Felipe comes for Ramona and takes her back to his mother’s estate. They then marry and have a family.

Ramona is largely a social piece about the mistreatment of Native Americans and the existence of prejudices within society. The main character Ramona belongs to both the Native American and white worlds, being of mixed race, with a Native American mother and an Irish father. However, her biracial heritage means her adopted family, represented by the Spanish Senora Moreno, can never fully accept her as she isn't full-white.

Ramona abandons her privileged life when she elopes with Native American farmhand Alessandro. Their relationship is troubled by outside racism. They cannot move to his village, as the whites have taken it over, and much the same happens everywhere else they go. In this way, we see that Ramona cannot settle comfortably into the Native American side of her heritage either, due to the settlement of the European and white Americans.

Ramona ends up losing everything. Her daughter with Alessandro dies from an illness since the local white doctor refuses to treat her. Alessandro goes mad from all their misfortunes and is shot when riding off with an American man's horse.

Ramona returns to the Moreno ranch to marry Senora Moreno's son Felipe, with her other daughter by Alessandro in tow. The two have many children after that.

Ramona is an evocation of Indian and Spanish life in early California. In the first half of the novel, Ramona, who is half Indian, half Scot and who has been reared by a Spanish matriarch, falls in love with Alessandro, son of a mission Indian. After a series of complications in the plot, the lovers triumph and, in the middle of the book, elope. Helen Hunt Jackson sets the common motives of greed, love, and pride in the context of differing ethnic backgrounds, treating the Spanish and Indian cultures with sympathy. For many readers, the appeal of the story lies in its first half, the romance.

In the second half, however, Ramona and Alessandro undergo a series of losses. They lose their land and their dignity, their difficulties leading finally to destruction. These losses occur because U.S. government policy encourages the American settlers to seize land from the Indians, and each removal from the land takes Ramona and Alessandro further from their cultural roots and from their natural sources of sustenance. As a result of these losses, they change from people with a rich cultural heritage and satisfactory material prospects to people with nothing. In this second part, Jackson presents her theme that government policy has systematically dispossessed the Native American tribes.

Two other characters round out Jackson’s picture of conflicting cultures: Señora Moreno, the Spanish matriarch, is a strong character. Aunt Ri, one of the American immigrants, is Jackson’s spokesperson. As Aunt Ri gets to know Ramona and Alessandro, she learns to understand and love them, even coming to their aid. She assails the Indian agent for the wrongs done to her friends and their people.

After Alessandro’s death, Felipe Moreno seeks out Ramona, marries her, and takes her to Mexico where they can have a better life. The novel is rich in local color, depicting a Spanish estate, sheep shearing, and the influence of the Catholic clergy. Although Jackson romanticizes life at the hacienda and in the early missions, the details are sufficiently vivid and accurate that early readers persistently sought to identify the particular estate that had been Ramona’s home.

Written to arouse public indignation at the treatment of the Indians, Ramona was a success. Some readers sympathized with its portrayal of the Indians; some resented its portrayal of Americans as land-grabbers. Readers bought out several printings between 1884 and about 1920. People made pilgrimages to Ramona’s presumed home, and at least three film versions followed. As popular enthusiasm waned, so did critical acclaim. Late twentieth century attention to the three cultures of the Southwest, however, revived interest in Jackson’s novel.