Ramona Ortegna, foster child of Señora Moreno, is much loved by all who live and work at the Moreno Ranch, except the Senora herself who cannot bring herself to think of the girl as anything but a mixed blood child. Half white, half Indian, Ramona had been adopted by Senora's sister who then entrusted the child to her upon her death. Already embittered by the loss to the Americans of much of her Southern California land as the result of the 1846 Mexican-American War, the pious old woman is also distraught by the near destruction of California's Catholic Missions. When a visiting Indian sheep shearer, Alessandro Assis, falls in love with Ramona and she with him, the two are forbidden to marry; the Senora's plan is to give Ramona to the Church. The lovers have no choice but to flee and find a safe place to shelter, work, and live their lives.

In 1881, author Helen Hunt Jackson wrote "A Century of Dishonor", a treatise that outlined the plight of Native Americans in California. Treated like slaves, robbed of lands that the Mexican government had given them rights to, they were further abused by the "land agents" the American government sent to aid them. When her book failed to capture the public's attention, the author decided to try fiction. "Ramona", her epic romantic novel, was a huge success. But it's important to note that the love story of Ramona and Alessandro and their perilous nomadic journey was based on real life incidents that Hunt Jackson discovered in her research.

The story still resonates: it has spawned four movies and an annual outdoor play which, in 2023, celebrated its 100th anniversary at the "Ramona Bowl" in Hemet, California.