The first sea expedition on the Tonquin left New York in September, 1810, stopped at Hawaii where a number of Native Hawaiian laborers were picked up, and arrived at the Columbia River in April, 1811, where Fort Astoria was established. The ship then sailed up the Pacific Coast to trade, but were taken over by the Tlaoquiaht tribe of Clayoquot Sound, Vancouver Island. The warriors killed 61 men before the ship was blown up by a surviving crew member.

About the same time the first sea expedition started, Astor also mounted an overland expedition in 1810-12. Called the Astor Expedition, it was led by Wilson Price Hunt and was the first overland expedition from St. Louis, Missouri to the mouth of the Columbia River after the Corps of Discovery, led by Lewis and Clark.

The party ascended the Missouri River as far as the Arikara villages near present-day Mobridge, South Dakota, then went west overland. Along the way the expedition discovered South Pass, Wyoming, through which hundreds of thousands settlers would later travel the Oregon, California and Mormon trails through the Rocky Mountains. When they continued on to the Snake River in southern Idaho. They abandoned their horses at Fort Henry and built canoes, but had to abandon this idea when they encountered a number of rapids. After two men and many of their food and supplies were lost, they divided into three main groups, each making their way to the Columbia River. Most of them arrived at Fort Astoria in the early part of 1812.

That year, the company suffered several setbacks, the first of which was the supply ship Beaver being late to arrive. The loss of the Tonquin vessel had left the post vulnerable at Fort Astoria found itself at risk of being captured by the British during the War of 1812. The following year, Fort Astoria and all other assets in the area were sold to the  North West Company.

Rocky Mountain Fur Company (1822-1833) - Sometimes referred to as Ashley's Hundred, the Rocky Mountain Fur Company was organized in St. Louis, Missouri in 1822 by General William Henry Ashley and Major Andrew Henry. They posted advertisements in St. Louis newspapers seeking "One Hundred enterprising young men . . . to ascend the Missouri River to its source, there to be employed for one, two, or three years." Among those hired were Jedediah Smith, William Sublette, Jim Beckwourth, Thomas Fitzpatrick and David Edward Jackson, just to name a few. Rather than relying on trading furs and pelts with the Indians, the Rocky Mountain Fur Company trained their men to do the trapping.