Manuel Lisa gained respect through his trading among Native American tribes of the upper Missouri River region, such as the Teton Sioux, Omaha and Ponca.

[citation needed] After he obtained a land grant in the Missouri area, they relocated to St. Louis, which was the center of the region's thriving fur trade, established primarily by French colonists, some also from New Orleans.

Polly Lisa lived in the city with their three children while her husband made his long expeditions to various Indian territories on the Upper Missouri River.

After being appointed US Indian agent in the area by the governor of the Missouri Territory, in 1814 Lisa married Mitane, a daughter of Big Elk, the principal chief of the Omaha until 1846.

He tried to gain custody of his children with Mitane, who let him take Rosalie back to St. Louis the next year for education at a Catholic school, but refused to let him have Christopher.

[11] In 1799, Manuel Lisa requested a land grant; according to his letter to the Spanish governor, Manuel wanted it "upon one of the banks of the River Missouri, in a place where may be found some small creek emptying into the said river, in order to facilitate the raising of cattle, and, with time, to be able to make shipments of salted and dried meat to the capital.

After being awarded the grant, Manuel Lisa and his wife relocated to St. Louis, where they purchased a home on Second Street near the Mississippi River.

[13] Having been stymied by the government and the Chouteau family, Lisa began organizing a trade expedition to the upper Missouri River region.

[3] On the first expedition, which departed in April 1807, Lisa and his company of 42 men (including John Colter, George Drouillard or Benito Vázquez) [14] moved up the Missouri until they reached the mouth of the Yellowstone River.

After ascending the Yellowstone some 170 miles (270 km), Lisa established a trading post on November 21 at the mouth of the Bighorn River in present-day Montana.

[3] In July 1808, after a successful trading season, Lisa departed Fort Raymond, leaving behind a small party of men for the winter.

[13] In the spring of 1809, Lisa returned to Fort Raymond with a major expedition, made up of 350 men, about half of whom were Americans, the rest French Canadians and Creoles.

They had 13 barges and keel-boats loaded with food, munitions, and articles suitable for the Indian trade, and the trip up the Missouri River was slow.

After Lisa's return to St. Louis in 1813, he heard fears expressed that British agents would encourage the upper Missouri tribes to attack settlements throughout the northern and western territories.

[13] The war disrupted the fur trade with the northern tribes on both sides of the border; in 1813 the British and American Indian allies burned Fort Lisa of North Dakota.

Early in 1814, William Clark, governor of the Missouri Territory, appointed Lisa as US Indian Agent to the tribes located above the mouth of the Kansas River, at an annual salary of $548.

He was especially effective among the Teton Sioux further upriver in present-day Minnesota,[25] whom he organized to send war parties against tribes allied with the British.

[13] While securing these alliances, in 1814 Lisa took Mitain as a consort; she was the daughter of Big Elk, the principal chief of the Omaha people.

(Lisa was still legally married to Polly, his first wife, but European-American men often took "country wives" among their Native American allies to build their relationships.

)[26] Later, the U.S. government recognized Lisa, calling his efforts as a "great service in preventing British influence" in the northern area.

He conducted them to Portage des Sioux to meet with the commissioners William Clark, Edwards and Auguste Chouteau to sign treaties of friendship.

Lisa and other Creole families pledged substantial funds to build a church (now called the Old Cathedral) near the river that was fit for the diocese.

By the time of his 1819 expedition, Lisa had developed strong relationships with the Omaha, Ponca, Yankton and Teton Sioux, Mandan and Arikara peoples.