After 1808 it was illegal for deep southerners to import slaves, and so they were brought down the Mississippi River from the North to the slave markets of Natchez and New Orleans.
This gave the northerners a way of selling off their difficult or troublesome slaves to the harsher plantation owners on the southern Mississippi.
It also meant that those selected or betrayed would be torn from their homes and families to be “sold down the river.”
When someone is betrayed we often say he was “sold down the river”.