Since the time of Columbus, explorers dreamed of a water passage across the North American continent. President Thomas Jefferson shared this dream. He conceived the Corps of Discovery to travel up the Missouri River to the Rocky Mountains and westward along possible river routes to the Pacific Ocean. Meriwether Lewis and William Clark led this expedition of 1804–6. Along the way they filled hundreds of notebook pages with observations of the geography, Indian tribes, and natural history of the trans-Mississippi West.

This last volume recounts the expedition's experiences as they continued their journey homeward from present-day Idaho and the party divided for separate exploration. Lewis probed the northern extent of the Louisiana Purchase on the Marias River, while Clark traveled southeast toward the Yellowstone to explore the river and make contact with local Indians. Lewis's party suffered from bad luck: they encountered grizzlies, horse thieves, and the expedition's only violent encounter with Native inhabitants, the Piegan Blackfeet. Lewis was also wounded in a hunting accident. The two parties eventually reunited below the mouth of the Yellowstone and arrived back in St. Louis to a triumphal welcome in September 1806.