Thomas Jefferson had long considered the project of a western expedition, having encouraged John Ledyard when he proposed such an expedition in the 1780s, and as president he contemplated the matter in earnest and discussed it with his private secretary, Capt. Meriwether Lewis. When Congress approved the plan in 1803 and appropriated money for it, Jefferson named Lewis to head it, and Lewis selected William Clark as his associate in command. The purpose was to search out a land route to the Pacific, to strengthen American claims to Oregon territory, and to gather information about the indigenous inhabitants and the country of the Far West. Before the long march was begun, the Louisiana Purchase was made, increasing the need for a survey of the West.

The men were gathered and in the winter of 1803–4 were trained in Illinois across the Mississippi from St. Louis, the starting point. In May, 1804, they set out up the Missouri, and the next winter was spent at the Mandan villages (near present Bismarck, N.Dak.). In 1805 the hardest part of the journey was made. After reaching the Three Forks of the Missouri River (and naming the three branches after Jefferson, Madison, and Gallatin in loyalty to the administration), they followed the Jefferson as far as they could. Then their Shoshone guide, the remarkable woman Sacajawea, helped to obtain horses for them to continue across the high Rockies. They crossed the Continental Divide at Lemhi Pass and went over the Bitterroot Mts. through Lolo Pass. They had reached the land of westward-flowing rivers, and for part of their way they followed the Clearwater River down to the Snake River (long called the Lewis). The Snake took them to the Columbia River and they spent a miserable, rainy winter season in Fort Clatsop, a crude post they built on the Pacific coast.

In the spring they started back across the continent. In July, 1806, the party split for a time in order to explore as much territory as possible. Lewis went with a group down the Marias River, while Clark and most of the men descended the Yellowstone River; they were reunited on the Missouri at the mouth of the Yellowstone on Aug. 12, 1806. The party arrived in St. Louis on Sept. 23, 1806, and were greeted with much acclaim. The route of the expedition is commemorated by a series of sites along the Lewis and Clark National Historic Trail (see National Parks and Monuments, table).

The importance of the well-planned, well-executed expedition (only one person had been lost) was enormous. Although it was not the first transcontinental crossing in the north (Alexander Mackenzie had preceded them in a remarkable voyage), it opened vast new territories to the United States. Its influence on the history of the West is incalculable. Its results matched the efficiency and capability of its leaders.