Lewis and Clark had reached the Three Forks of the Missouri, which they named the Jefferson, the Madison, and the Gallatin, on July 27, 1805. Beyond lay the major obstacle in their journey to the Pacific, the passage over the Rocky Mountains to some navigable tributary of the Columbia River. To make this trip they needed the assistance of the Shoshone Indians, Sacagawea's people, and although they had seen signs indicating the presence of these people, none of them had yet appeared.

What Lewis and Clark hoped to find was the "pyramidal height of land," the point from which, geographical theorists believed, the great rivers of the West flowed toward the Pacific, the Gulf of Mexico, and the Gulf of California. It would be, in 1805, the closest thing still possible to the Northwest passage that so many mariners had yearned and searched for, that James Cook had sought less than thirty years before, and that Alexander Mackenzie had failed to find in the previous decade but had thought might exist somewhere in the continent. The information supplied by the Mandans and Hidatsas suggested there might yet be an easy portage to the Columbia headwaters.

The captains decided to proceed up the Jefferson, the westernmost fork, with Lewis going ahead with a few men to search for the Shoshones. Clark, unable to do much walking because of illness and a bad boil on his ankle, would command the main party in the canoes. The passage of the canoes became increasingly difficult as the streams became more shallow and unnavigable because of rapids. Much of the time the men had to draw the canoes along by hand, wading in the water. The party moved on up the Jefferson and then its main tributary, the Beaverhead. Lewis proceeded ahead, past the forks of the Jefferson and such landmarks as Beaverhead Rock. He left a message for Clark to take the Beaverhead River instead of the west fork, which they named Wisdom River (today's Big Hole River), but a beaver chewed down the pole on which he left the message and Clark took the wrong fork, causing another day's delay.

Lewis was amazed that the rivers penetrated so far into the mountains while still being navigable, but he knew that this situation would not long continue. On August 10 he reached the forks of the Beaverhead River and followed the western fork into the valley the captains later called "Shoshone Cove." The next day, following an Indian trail, the advance party came upon a Shoshone on horseback. Lewis tried to convince him by signs that they were friend, but the Indian evidently feared they were Blackfeet raiders and fled.

On August 12 Lewis and his three men continued following Indian paths up later Trail Creek. At the head of that stream they reached what they considered the source of the "heretofore deemed endless Missouri." A short distance beyond was the ridge of the Continental Divide. From this vantage point Lewis could look west and and see further ranges of mountains—proof that the portage to the waters of the Columbia would not be as easy as he had hoped. His immediate problem, however, remained that of making friendly contact with the Shoshones.

Lewis's party had crossed Lemhi Pass into Idaho, the first U.S. citizens to traverse the Continental Divide. On August 13 they continued down into the valley of the Lemhi River, still following the Indian trail. Once again they encountered some Indians, who fled at their approach. Finally they found a woman and two girls who did not see them until they were quite close. One of the girls fled, but the woman and the other girl apparently thought it was too late to run and sat waiting for the strangers to kill them. Lewis took the woman's hand, repeating the word "ta-ba-bone," which he evidently obtained from Sacagawea and which he thought meant "white man." He rolled up his sleeve to show his white skin and gave the two Shoshones presents. Somehow he calmed them and, through George Drouillard's sign language, persuaded them to call back the girl who had fled before she could raise an alarm in the main Shoshone camp.

Through these three Shoshones Lewis was able to make contact with their people who were camped on the Lemhi River. The chief, Cameahwait, seemed friendly, but his people were still afraid that the strangers were in league with the Blackfeet and would betray them into the hands of their enemies. Lewis, trying to persuade them to go with him to meet Clark's party on the Beaverhead River, feared that they would take alarm and disperse into the mountains, where he knew that he would never find them, and that his command would be left stranded in the mountains with winter coming on. To prevent this he used every form of persuasion he could think of, including promises that white traders would follow him and would provide the Shoshones with trade goods, such as guns to use against their enemies. He gave the chief his own gun, saying that Cameahwait could shoot him if he proved unfaithful. Recovering a message he himself had left at the forks of the Beaverhead for Clark, he stalled for time, saying it was a message from Clark that the main party would soon be there. These means, along with stories about a man with black skin and another with red hair—wonders that greatly intrigued the Indians—persuaded them to wait at the forks until Clark's party arrived on August 17. Such was the captains' relief that they called the campsite at the forks of the Beaverhead "Camp Fortunate."

Geographical information obtained from the Shoshones was not encouraging. A reconnaissance by Clark confirmed that the principal streams in the vicinity, though they did flow toward the Columbia, were unnavigable because of rapids. The only alternative was to obtain horses from the Shoshones and cross the mountains by land. Fortunately, they secured the services of an Indian they called "Old Toby," who knew of a route over the ranges. The latter part of August and much of September would be consumed by the overland trek, which would take them back into Montana, then back to Idaho, and would include a journey over the rugged Lolo Trail. Along the way they met the Flathead Indians, another tribe who had never seen white men.

The trip over the Bitterroot Mountains via the Lolo Trail was perhaps the severest test of the whole expedition. Winter was already beginning in the high country in September, and the party would struggle through deepening snow. Lack of game forced them to kill and eat some of their horses. Pack animals slipped and fell down steep mountainsides. Old Toby misled them at one point, costing even more time. Finally the captains decided to adopt their old procedure of sending one of the officers ahead with a small party to find open country and make contact with friendly Indians. Accordingly, Clark set out with six men on September 18 and two days later reached Weippe Prairie, an open area in west-central Idaho, where he was the first white man to meet the Nez Perce Indians. The long and difficult trip from mountain pass to meadows dashed all hope of a short portage across the Rocky Mountains and ended dreams of an easy passage to the Orient.

The Indians offered the party roots to eat, but the food proved a mixed blessing, for it caused indigestion and diarrhea among most of the Corps' men. In spite of their suffering they established a camp on the Clearwater River and began building dugout canoes for the trip to the Pacific. On October 7 they were ready to start out, leaving their horses with the Nez Perces to await their return.

The Clearwater flows into the Snake and the Snake into the Columbia. Following these streams, the Corps passed out of the mountains down to the Great Columbian Plain. The party had traveled through a variety of ecosystems previously unknown to Anglo-Americans. From the Great Plains, semi-arid and largely treeless yet teeming with game, they had entered the Rocky Mountains, the first English-speaking whites to do so with the exception of Alexander Mackenzie's Canadian party to the north of a few years earlier. In the mountains they found a region heavily wooded in many places, where the game necessary for sustenance was scarce and the natives often lived on the edge of starvation. Even so, they encountered unfamiliar species at every turn. They saw the birds that would bear the captains' names, Lewis's woodpecker and Clark's nutcracker. They were the first whites on record to examine the hide and horns of the mountain goat, and Clark caught a distant sight of one, although the party would never obtain a full specimen. In traversing the mountains they saw new trees such as grand fir and lodgepole pine. On the western side of the mountains they found the camas root, a vital element in the diet of tribes like the Nez Perces. Their own diet shifted drastically as they passed from the abundance of buffalo and elk on the plains to the scarcity of the mountains. They supplemented the increasingly scarce deer with roots and with the flesh of their own horses. The changes sometimes had drastic effects on their health.

Coming down to the Columbia Plain, they again entered a new world, barren of trees like the Great Plains but also barren of game. They shifted from an area inhabited by horseback tribes who hunted on the plains east of the mountains to tribes who traveled by canoe and subsisted on salmon and roots. They were able to observe the end of the great salmon run on the Columbia, the numbers of which Clark found "incredible to say." The steelhead trout appeared near the falls of the Columbia. Clark thought he saw a sea otter, but this mammal never leaves salt water and the creature sighted was probably the harbor seal, another species new to Anglo-Americans.

The captains had expected to find rapids and falls on the Columbia, and they did. They reached the Celilo, or Great, Falls on October 22, and beyond them lay the Cascades, passing through the mountain range of the same name. They portaged some of these obstacles and, to save time, ran through some others, lowering the canoes with elkskin ropes. Beyond the Cascades lay the final run to the Pacific Coast, which they had come so far to reach.