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Boone County was organized November 16, 1820, from a portion of the territorial Howard County. The area was then known as Boone's Lick Country, because of a salt lick which Daniel Boone's sons used for their stock.
Boone County was settled primarily from the Upper South states of Kentucky, Tennessee and Virginia. The settlers brought slaves and slave-holding with them, and quickly started cultivating crops similar to those in Middle Tennessee and Kentucky: hemp and tobacco. Boone was one of several counties to the north and south of the Missouri River that was settled by southerners. Because of its culture and traditions, the area became known as Little Dixie, and Boone County was at its heart. In 1860 slaves made up 25 percent or more of the county's population, Boone County was strongly pro-Confederate during the American Civil War.
Shortly after the murder of President Lincoln, the leading citizens of the county denounced the killing. They also directed that all public buildings including the courthouse and the university be draped in mourning for thirty days.