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In 1843, a wagon train led by widowed Sen. William J. Tadlock leaves Independence, Missouri, for the long trek across the Oregon Trail. Foremost among the settlers are: Dick Summers, a seasoned trail scout with failing eyesight; farmer Lije Evans, his wife Rebecca, and their 16-year-old son, Brownie; newlyweds Johnnie and Amanda Mack; Sam Fairman and his wife, who are awaiting the birth of their child; and the slovenly McBee family. After several weeks on the trail, Johnnie, frustrated by his bride's frigidity, makes love with the flirtatious Mercy McBee during a drunken celebration; later that night, he shoots at what he thinks is a wolf and kills the son of a Sioux chief. Tadlock tries to evade the vengeful Indians by driving the wagon train into a buffalo herd, but the settlers are overtaken, and he is forced to hang Johnnie as retribution for the slaying. Mercy, pregnant with Johnnie's child, then accepts Brownie's offer of marriage. During a cattle crossing, Tadlock's son is killed in a stampede, and the senator is so disgusted by his own resulting emotional breakdown that he orders his Negro slave to whip him. In time, the settlers tire of the hardships and consider changing course from Oregon to California; to avert this, Tadlock fakes a smallpox scare, forcing the Army to order the train into the open plains. The lie is eventually exposed, and Lije attacks Tadlock savagely and assumes command. Eventually the caravan reaches its destination, with only a deep gorge remaining to be crossed. When Rebecca Evans shows the settlers Tadlock's design for a great city in Oregon, the ostracized leader is welcomed back into the group and permitted to supervise the lowering of people, animals, and dismantled wagons down the steep ravine. As the senator descends the cliff, however, Amanda Mack, driven to insanity by her husband's hanging, cuts the rope, and Tadlock plummets to his death. After his burial, the settlers journey down the Columbia River, leaving Summers behind.