After braving the Oregon Trail and settling near the Columbia River, Protestant missionaries Marcus and Narcissa Whitman seek to spread their Christian faith and bring their way of life to the local Cayuse people. But their struggle to adapt to their new world, and a devastating outbreak of measles, heightens fears and tensions both with the Cayuse, and each other, setting up a tragic encounter with historic consequences.

In Gold Rush California, Mexican immigrant Joaquin Murrieta forms a gang of outlaws that spreads terror across the newly formed state.