The history of Boonville begins in a region where the Missouri River divided Indian power, with the Osage dominating south of the river and the Ioway, and later the Sauk and Fox, holding power to the north. River bluffs preserved pictographs and ancient burial mounds, while the nearby Missouri tribe was devastated by smallpox and attacks by the Sauk, and survivors joined the Oto upriver. In 1805, Daniel Boone's sons began making salt at Boone's Lick, a business later continued by the Morrisons despite dangers from conflict and the War of 1812. Settlement in the Boonslick expanded after treaties opened Osage land, though war interrupted growth. Franklin became the first town in 1816, and Boonville, laid out in 1817 on higher bluffs, soon gained importance as Cooper County's seat and as a safer site from flooding. Steamboat traffic after 1819 helped Boonville rise as a port after Franklin was washed away, linking the area to wider trade despite the river's hazards. By 1861, agriculture, trade, steamboat access, manufacturing, slavery-based tobacco and hemp production, and German wineries and breweries had made Boonville a thriving center. That year, one of the first Civil War battles in Missouri occurred just east of Boonville, where Union forces under Gen. Nathaniel Lyon defeated Confederate forces led by Col. John Marmaduke and secured Union control of the Missouri River. Later, railroads connected Boonville to wider markets and reduced the Missouri River and the Boonslick region's former central importance.