St. Louis was founded as a trading post in 1764 by Pierre Laclède, a fur trader of New Orleans, and René Auguste Chouteau. There were many French traders still in the region, although the east side of the Mississippi River had become British and the west side Spanish; they preferred dealing with St. Louis rather than traveling to the French Canadian posts. The land east of the river became part of the United States as a result of the Revolutionary War, and American traders were eager to move on westward. Both in America and in Europe the emergence of a large merchant-professional class vastly increased the demand for the fashionable beaver hat.

The Americans' opportunity to expand westward came when the United States in 1803 purchased Louisiana. The government was granting very few licenses to private traders, hoping rather to handle all fur trade through government trading houses located at army posts. This system had little success, however. Private traders working out of St. Louis were already dealing with the Osage, Ponca, and Mandan Indians.

In 1804 the Lewis and Clark Expedition, sent out by President Thomas Jefferson to explore the territory of the Louisiana Purchase, left St. Louis to journey up the Missouri River and on to the Pacific coast. The exploring party was followed almost immediately by fur traders, notably Manuel Lisa of St. Louis. When the explorers were returning in 1806, John Colter, a member of the group, left them to join Lisa in the fur trade. Lisa, Jean Pierre Chouteau, Andrew Henry, and their associates in 1809 formed the St. Louis Missouri Fur Company, which had posts throughout the Missouri River valley.

John Jacob Astor, an American fur trader in New York City, had founded the American Fur Company in 1808 to operate in the upper Great Lakes region. In 1810 Astor established a post, Astoria, on the Pacific coast at the mouth of the Columbia River, which had been discovered by the American sea captain Robert Gray in 1792. Meanwhile a Canadian firm, the North West Company, had spread from the Great Lakes to the Pacific coast. Rivalry with the Hudson's Bay Company ended in 1821 with North West being taken over by Hudson's Bay. Meanwhile Astor had built up a monopoly in the Great Lakes fur trade.

The trade of the Missouri River and the West gradually changed in character. In 1810–11, Andrew Henry and a party of trappers spent the winter west of the Rocky Mountains. The winter pelt of the beaver was far superior to that of other seasons, but the Indians would not trap in bitter cold weather. Much of the trapping was therefore taken over by white men, who gained the name “mountain men.” In 1822 Henry and William Henry Ashley formed the Rocky Mountain Fur Company. Among the mountain men employed by them were Jed Smith, Bill Sublette, and Jim Bridger. Other well-known trappers of the era included Kit Carson, Joe Walker, and Tom Fitzpatrick.

A new system of collecting furs from trappers and Indians was set up in 1825—an annual rendezvous held somewhere in the Rocky Mountains. Often the white trappers spent their full year's earnings on supplies and a week of wild living before heading back into the mountains for another year. Some Indians were hostile, and fortified trading posts were a necessity. Among these were Fort Laramie in Wyoming and Bent's Fort in Colorado. After Mexico gained its independence from Spain in 1821, there was some fur trade with Santa Fe.

By the end of the 1830's the beaver was virtually trapped out. The beaver hat, however, was rapidly going out of style, replaced by the silk hat. Although there was still a market for pelts of small animals and for buffalo hides, the colorful era of the mountain men came to an end. They would always be remembered, however, among the explorers and pioneers who opened up the American West to settlement.

Meanwhile, a sea-based trade in fur-bearing marine animals had been flourishing along the Pacific coast. It was begun by the Russians, who crossed the Bering Strait to Alaska in 1741 and found sea otters and fur seals plentiful in the region. The native Aleuts did the hunting and the Russians sold the pelts in China, where otter fur was prized above any other kind. The Spanish in California soon joined in the otter and seal trade, getting pelts from Indians.

This rich trade with China was unknown to the English-speaking world until Captain James Cook sailed to the west coast of North America in 1776. After the Revolutionary War American ships began to trade with China, and their crews wanted to join in the fur trade, but found their access to pelts largely blocked by the Spanish and Russians. Captain Gray was successfully engaged in this trade, however, when he found the entrance to the Columbia River.

In the early 1800's it became convenient for the Russians, who lacked a base in the area, to make an arrangement with the Americans by which Aleuts, furnished by the Russians, would hunt in California waters in American ships. The venture was so successful that in 1812 the Russians decided to take all of the profits for themselves by eliminating the need for American ships. With this in mind, they established Fort Ross on the California coast to serve as a base for their Aleut hunters.

When Mexico became independent, it permitted both Russians and Americans to hunt off California, in return for half the profits. Otters and seals were virtually exterminated by the time California was ceded to the United States in 1848. Meanwhile Alaska's supply of fur-bearing sea animals was becoming so depleted that Russia lost interest in the territory and later sold it to the United States. Otter and seal hunting was regulated by international treaty in 1911.

Buffalo hides with the hair left on were widely used as carriage robes and, in frontier areas, floor coverings. Buffalo hide also made an especially sturdy leather. The supply of buffalo seemed inexhaustible, but by the mid-1800's there were none left east of the Mississippi River. The value of buffalo hides was modest compared with the price commanded by fine furs, however, and the buffalo trade did not attract white hunters. Indians provided whatever quantity the traders specified.

As the population of the United States and Canada increased, the demand for buffalo robes and leather grew also. After the Civil War in the United States, white hunters traveled to the regions of the great buffalo herds, often by railroad, and slaughtered the animals by the thousands. As the herds dwindled, the Indians sought out the remaining bands, primarily as food for themselves but also to have hides for trade. By 1885 the buffalo were virtually wiped out, and the large-scale killing of wild land animals for their fur or hide was finished in North America.