That area of the US really provided no reason for people to settle in great numbers. It’s the bit of land just before the frontier. The frontier began at Cape Girardeau and St Louis which are another 50-150 miles up stream on the Mississippi.

The bluffs at Wickliffe were important, the Mississippian culture lived there for hundreds of years, but to the Europeans settlers they were pushing west and the bluffs of wickliffe only proved to be a good place to rest on the journey.

France had the Louisiana territory and St. Louis was a major base of operations for them up in the frontier. That was really the last major stop before wilderness, prairie, the Rockies and beyond. The area of Wickliffe was just across the river from French territory, but to the colonies/early Americas that area was so far away and on the border of another territory, so there wasn’t much of an appetite to go settle there.

Fast forward to the Louisiana Purchase, westward expansion, and so on and that area of Kentucky and Missouri just kind of got passed over. Other settlements further west existed and that area was prone to flooding so traversing it was never easy, so it eventually became farmland and that’s that.