The son of either Cuban or Spanish parents, Lisa was born in New Orleans in 1772. By the time he was a young man he had developed extensive trading interests along the Mississippi River, and in 1799 he chose St. Louis as the center of his growing business. When the explorers Meriwether Lewis and William Clark came to St. Louis in 1804, Lisa sold them many of the supplies required for their long journey to the Pacific.
When Lewis and Clark returned to St. Louis two years later, Lisa listened with interest to their reports of rich beaver and otter populations to be found in the upper Missouri River country. Lisa quickly began to organize a fur trading expedition, and in 1807, he headed up the river in a keelboat. Overcoming opposition from several Indian tribes along the way, Lisa managed to reach the confluence of the Big Horn and Yellowstone rivers in present-day Montana. There he established the Fort Raymond (later Fort Lisa) post and began providing Indians with manufactured goods in exchange for furs.
The potential for the upper-Missouri River fur trade was huge, and initially Lisa’s business thrived. In 1809, several prominent St. Louis men (including Lewis and Clark) joined with Lisa to form the Missouri Fur Company. The company ran into trouble, however, with the Blackfeet Indians of Montana, who resented Lisa’s challenge to their long-standing dominance of the area fur trade. The War of 1812 further undermined the business, and in 1814, the Missouri Fur Company dissolved.
Lisa continued to trade for furs on the Missouri, enjoying several successful years and establishing excellent relations with the Omaha tribe by marrying one of its women. Lisa made his final trip up the Missouri in 1819, but when he returned he was suffering from an unidentified ailment that eventually proved fatal. He died in St. Louis in 1820 at the age of 47. Though his life was cut short, he had already explored vast new areas of territory and established the basic methods that would be used by the fur trade for decades to come.