[5] Greenville was named after Fort Greene Ville (now Greenville), Ohio, the site where General Anthony Wayne signed a treaty with the Native Americans after defeating them in the Battle of Fallen Timbers on August 20, 1794.

Confederate Brigadier General William J. Hardee and officers Patrick Cleburne, Thomas C. Hindman, and Basil W. Duke along with about 800 men were stationed close to Greenville near the outset of the Civil War until they began to retreat to Randolph County, Arkansas on August 28, 1861.

On July 20, 1862, a camp of two companies of the 12th Missouri State Militia was attacked at daylight, surprising the camp, taking most of their rifles, 16 Savage revolvers, all of their horses, 50 pairs of holster pistols, and killing four of their men.

In 1941, the village was relocated two miles to the north after the construction of Lake Wappapello.

[8] Greenville is located on the southern edge of the Ozark Mountains, situated in a hilly, forested landscape.

According to the United States Census Bureau, the city has a total area of 0.68 square miles (1.76 km2), all land.

[9] Greenville is on the east shore of Lake Wappapello, on the St. Francis River.

[10] The Greenville R-2 School District runs throughout most of eastern Wayne County.

The single local newspaper is the weekly Wayne County Journal Banner.

34.4% of all households were made up of individuals, and 16.7% had someone living alone who was 65 years of age or older.

The racial makeup of the city was 98.67% White, 0.22% Native American, and 1.11% from two or more races.