As part of their colony known as La Louisiane, the French established a settlement at what became Natchez, Mississippi.

The first, (known as Old Greenville) located to the south near Natchez, was the Jefferson County seat from 1803-1825[4] but became defunct soon after the American Revolution, as European-American settlement was then still concentrated in the eastern states.

Many migrants came to the area of the future, second Greenville, located approximately 150 miles north of the first Greenville, from the eastern and Upper South states, seeking land for developing cotton plantations, and this area became a trading center for the region's plantations.

[5] American William W. Blanton filed for land from the United States government and was granted section four, township eighteen, range eight west; this plot now constitutes most of current downtown Greenville (the third).

This Greenville was thriving hamlet in the antebellum years, as cotton plantations developed in the area generated high profits for major planters.

[6] As county seat, Greenville was the trading, business, and cultural center for the large cotton plantations that surrounded it.

When the war ended, veterans of Mississippi regiments returned to find Greenville in a state of ruin.

They chose a new site (the third, current Greenville) three miles away, at the highest point on the Mississippi River between the towns of Vicksburg and Memphis.

She welcomed the idea of a new Greenville, and donated land for schools, churches and public buildings.

Major Richard O’Hea, who had planned the wartime defense fortifications at Vicksburg, was hired to lay out the new town.

Greenville recovered prosperity, still based on cotton, despite the decline in world markets for this commodity.

In the early 20th century, its elite families had considerable political influence in the state, and US Senator Leroy Percy was from here.

Several residences and other buildings from the late 19th and early 20th centuries have been listed on the National Register of Historic Places.

[8] In the early 21st century, the Mississippi Blues Commission was established to commemorate this music in the state's history and culture.

Southern Whispers Restaurant on Nelson Street in Greenville was the second site identified on this trail; this was a stop on the Chitlin' Circuit in the early days of the blues.

The historic marker in front of the restaurant commemorates its importance in the history of the blues in Mississippi.

Commercial passenger air service is currently provided by Contour Airlines with nonstop Embraer regional jet flights to Dallas/Fort Worth (DFW) and Nashville (BNA).

[42] The Greenville Higher Education Center offers non-credit community courses and credit courses from Delta State University, Mississippi Delta Community College (MDCC), and Mississippi Valley State University.

The people in this region were influenced by the larger Mississippian culture, which built similar ceremonial sites throughout the Mississippi Valley and its tributaries.

The historic Natchez people are considered the only contemporary surviving group of the Mississippian culture at the time of European exploration.

A museum on the grounds displays artifacts recovered in professional excavations and adds to the interpretation of this complex, and the park has walking trails.