During the US expansion into Indian Territory, a doctor, an Indian chief and a senator deal with the upheaval. While the chief fights for his people, the senator ensures a humane treatment for them.

In the 1880s, after the U. S. Army's defeat at the Battle of the Little Bighorn, the government continues to push Sioux Indians off their land. In Washington, D.C., Senator Henry Dawes introduces legislation to protect Native Americans rights. In South Dakota, school teacher Elaine Goodale joins Sioux native and Western-educated Dr. Charles Eastman in working with tribe members. Meanwhile, Lakota Chief Sitting Bull refuses to give into mounting government pressures.

Bury My Heart at Wounded Knee is a somber retelling of the true events leading up to the massacre at the Wounded Knee Creek in southwestern South Dakota on December 29, 1890.