Many times Boone interacts with the Cherokee while he is at Boonesborough. Boonesborough is in northern Kentucky, while the Cherokee were never closer than the southeastern tip of Tennessee. Boone did fight with the Cherokee during the French and Indian War from 1754-1763 when he lived in North Carolina. Boonesborough was founded in 1775 by Boone.
Throughout the series, there are many historical inaccuracies in the depictions of Daniel Boone's recorded life.
This series help promote the myth that Daniel Boone and Davy Crockett were one and the same person. In fact, the producers had intended the show to be about Crockett, but Walt Disney would not sell them the rights, so they used the name Daniel Boone instead.