This area was occupied by indigenous peoples for thousands of years. When the French explored here, they encountered the historic Natchez people. As part of their colony known as La Louisiane, the French established a settlement at what became Natchez, Mississippi. Other Native American tribes also lived in what is now known as Mississippi.
The current city of Greenville is the third in the State to bear the name. The first, (known as Old Greenville) located to the south near Natchez, became defunct soon after the American Revolution, as European-American settlement was then still concentrated in the eastern states.
The second Greenville was founded in 1824 by American William W. Blanton, who filed for land from the United States government. He was granted section four, township eighteen, range eight west. This plot now constitutes most of downtown Greenville. It was named by its founders for General Nathanael Greene, friend of President George Washington, for whom the county was named.
Many migrants came to the area from the eastern and Upper South states, seeking land for developing cotton plantations. In 1830 the United States Congress passed the Indian Removal Act, which authorized the government to make treaties to extinguish Native American land claims in exchange for lands west of the Mississippi River. They forced most of the Southeastern tribes to Indian Territory during the following decade.
The second town was thriving hamlet in the antebellum years, as cotton plantations developed in the area generated high profits for major planters. They built their wealth on the labor of enslaved African Americans.
Greenville was designated as the county seat in 1844. It had become a trading center for the region's plantations. The two previous county seats, New Mexico and Princeton, had also been located along the Mississippi River, and had been eroded by the waters, to the point that they were destroyed.[3] As county seat, it was the trading, business, and cultural center for the large cotton plantations that surrounded it. Most plantations were located directly on the Mississippi and other major navigable tributaries. The interior bottomlands were not developed until after the Civil War.