Conveniently, just a few days ago, I wrote a post on Spain's failed attempts to settle further north.

One I didn't mention there was Juan Pardo's attempt to colonize the Carolinas in 1566-68. He started out by establishing the colony of Santa Elena near what's now Port Royal, SC, and later headed inland to construct Fort San Juan near Morgantown, NC, and a for additional forts in the surrounding area. At the time, this part of Joara, a Mississippian chiefdom. After receiving reports of a potential French invasion of Santa Elena, Pardo left to reinforce the town, leaving Hernando Moyano in command of 30 men at Fort San Juan. While Pardo was away, Moyano joined with Joaran forces to attack Chiscas and Chiaha, now in Tennessee. At Chiaha, Moyano established another fort.

The garrisoned Spanish soon began making onerous demands on the local populations. By the time Pardo returned to resupply and garrison fresh troops in all the newly established forts along the Tennessee-North Carolina border, he was stretching his forces too thinly in a region that did not want them there. In the spring of 1568, an uprising occurred that left only one Spanish survivor and burned all the forts. After this failure (in a long serious of failures), the Spanish lost interest in colonizing the interior. Santa Elena itself would last a bit longer, until it too was destroyed the combined forces of Orista and Escamacu (little known Cusaboan peoples) in 1567. A few additional attempts were made to establish a colony at the site of Santa Elena, but they were likewise repelled.