Indigenous tribes in the region included the Wyandot, the Delaware, the Shawnee, the Ottawa, the Chippewa, the Pottawatomi, the Miami, the Wea, the Kickapoo, the Piankasha, the Kaskaskia and the Eel River.

Greenville is the historic location of Fort Greene Ville, built in November 1793 by General Anthony Wayne's Legion of the United States during the Northwest Indian War.

Named for Revolutionary War hero Nathaniel Greene, its defenses covered about 55 acres (220,000 m2), making it North America's largest wooden fort.

It was a training ground and base of operations for the ~3000 soldiers of the Legion and Kentucky Militia before their August 1794 march northward to the Battle of Fallen Timbers.

A year after the battle, the Treaty of Greenville was signed at the fort on August 3, 1795, with chiefs of the tribes that had confronted the U.S.

This brought an end to the Indian wars in the area and opened the Northwest Territory for European-American settlement.

[6] In 1805[7] or 1806,[8] the Shawnee chief Tecumseh and his younger brother Tenskwatawa established an illegal settlement in Greenville.

[7] The Army abandoned Fort Greenville in 1796; it was partly burned later that year to retrieve nails used in its construction.

Local settlers carried away some of its logs for building the new settlement of Dayton, Ohio, to the south.

In the War of 1812, the Army refitted what remained of the fort; it was used as a supply depot and staging area.

Greenville hosts the Darke County Fair, which runs annually for nine days in August.

[19] Over three days in 2006, 18 men were arrested, with Darke County officers assisting the Dateline NBC crew.