It was too difficult, since it was easy for locals that knew the land to just run away and take refuge with other tribes. In Florida, some black slaves notoriously ran away and joined the Seminoles, a tribe that led a pretty notable resistance for sovereignty. This is a simplification, another big factor would have been the fact that many tribes had already established themselves as political entities, expect the five civilized tribes, via trade and intermixing. I would hazard that many white people from the south and southeast would have some native ancestry. Finally, when all blacks we're defacto slaves and free blacks were uncommon, it was easier to identify a run-away. In fact several Southeastern tribes owned slaves themselves and the Cherokee were actually split in their support for the Union vs the Confederacy.
When the Europeans settled in the Carolinas, they brought malaria with them. The ensuing epidemic affected both the natives and the settlers (and malaria, with lethargy as its major symptom, is especially bad for a manual labor force). People of West African descent tend to have a very strong resistance to malaria that's related (in a way I don't understand) to the sickle-cell gene. Since the ships trading back and forth across the Atlantic were also trading to the western coast of Africa (and exchanging sailors/slaves/passengers at all stops), eventually some west African laborers ended up in the carolinas, and someone noted that they were unaffected by malaria.
The eventual presence of large groups of west african laborers, combined with a tradition/economy of chattel slavery among the Carolina natives that predated the settlers to create a very economically effective slavery system that spread across the southern US.
South Carolina was founded as a rice-growing colony to supply food to the sugar-growing colonies in the Caribbean. They bought enslaved agricultural workers from west Africa because they had the skills to grow rice more effectively. Rice wasn't native to the Americas, so buying natives wouldn't have resulted in the significantly higher rice yields.
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sidenote: They also bought people who knew how to cultivate indigo for dyes. This meant that indigo was the dye most-available for the continental army in 1775.
