When Army scout and mountain man, Zeb Macahan (James Arness) comes home to Virginia after being away for ten years, his family is worried by talk of the imminent United States Civil War. Zeb's brother Timothy (Richard Kiley) and Timothy's wife, Kate (Eva Marie Saint), decide to move west.

During the United States Civil War, army scout Zeb Macahan (James Arness) returns to Virginia to help his brother's widow, Kate (Eva Marie Saint), and her three children, Luke (Bruce Boxleitner), Josh (William Kirby Cullen) and teenage daughter, Laura (Kathryn Holcomb), decide to move West to Oregon Territory. The trek proves far more arduous and dangerous than they expected as the Macahans struggle to survive an unforgiving land and Native Americans who are fighting to survive an invasion of white settlers to their land. Headed for Oregon, the Macahans stop along the Platte River in Nebraska territory. Bounty hunter Martin Grey (Anthony Zerbe) arrests Luke for desertion from army; Zeb rescues Luke; but Luke is shot while protecting Erika Hanks (Brit Lind), a member of a religious sect called the Simonites.

The Simonites prevent a shoot-out between Zeb and Grey by standing between the two men. Grey rides away, and Erika brings Zeb to Luke's hiding place, where Luke states his wish to remain with the Simonites. Zeb leaves Luke to find an old friend, Cully Madigan (Jack Elam), who admits to killing Arikara Indians who kidnapped his young son and attacked his Indian wife. Zeb joins Cully in his search for the boy, but as they travel through the mountains, they are captured by Crow Indians. The Arikara, enemies of the Crow, release Zeb and the boy in exchange for Cully, and as the two ride away, they hear the shouts and war cries of the Indians as the torture of Cully begins. At the Simonite settlement, Luke is confronted by the father and two brothers of the man he killed while protecting Erika. They threaten to shoot Erika's father unless Luke surrenders, and once more, Luke kills.

Zeb leads Cully's son to safety and returns to the Arikara Indian camp to fire a merciful bullet, killing Cully instantly. While the Macahan family is under attack by hostile Indians, Erika joins Luke on the trail. But the lovers are ambushed by the remaining gunmen, and in a gunfight with Luke, the outlaws and Erika are both killed. Luke rides to the town of Devil's Gap to get drunk. In a saloon girl's bedroom, he says too much, and the girl turns him in for the reward. Zeb rides to Devil's Gap posing as a U.S. Marshal and gets Luke released to his custody. Learning of the trickery, bounty hunter Grey forces the local sheriff to form a posse. Zeb and Luke are chased by the posse. Grey, however, rides directly to Kate's farm, where he holds the family hostage and surprises Zeb and Luke when they arrive. Kate kills the bounty hunter in defense of her family. September, 1865--the Macahans finally head west from the Platte River for Oregon.

Kate Macahan's sister, Molly Culhane from Chicago, joins the family. A Mormon family arrives at the homestead while fleeing religious persecution, but the patriarch soon charms Laura. Zeb mediates between the Army and the angry Sioux after Russian royalty kills buffalo on Sioux land. Luke aids a local sheriff and meets his feisty daughter.

Zeb sides with the Sioux after the Russian incident triggers a war - and the clash leads to a great leader's sacrifice. Luke's feelings for Hillary Gant intensify, but when her father learns of Luke's past, he asks Luke to leave. Laura accepts a marriage proposal, while Luke finds himself forced to join a thieving band of ex-Confederates.