When Kansas becomes a battleground in the national debate over slavery, settlers on both sides of the issue pour into the territory to determine its future.

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

The abduction of nine-year-old Cynthia Ann Parker kicks off a series of increasingly deadly confrontations between her Comanche captors and the newly independent Texas. As the Comanche grow ever more desperate to protect their lands from Texan incursions, Cynthia Ann's eventual rescue sees her violently removed from her new native family, and dropped back into a seemingly hostile foreign culture, while pushing her son - the last Comanche leader - on a campaign of revenge that will ultimately bring down their empire.

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.

After building his reputation as a formidable hunter on Lewis and Clark's Expedition into the newly acquired Louisiana Territory, John Colter chooses to stay out in the wilderness and enter the booming fur trade. But when he repeatedly ignores warnings from the Blackfeet not to hunt their sacred beaver on their lands, he's taken captive and forced to make a run for his life.

Following years of land encroachments by American settlers, Chief Little Turtle of the Miami leads the Indian Nations of the Northwest Confederacy to a major victory over the fledgling U.S. Army. But a new force under General "Mad" Anthony Wayne embarks on a counteroffensive, leading to a final battle that will see the Confederacy defeated – and open a new era of westward expansion.