Much of the original city is contained within the boundaries of the Milledgeville Historic District, which was also added to the NRHP.

In 1803 an act of the Georgia legislature called for the establishment and survey of a town to be named in honor of the current governor, John Milledge.

The Treaty of Fort Wilkinson (June 1802) had recently forced Native American tribes to cede territory immediately west of the Oconee River.

The new planned town, modeled after Savannah and Washington, D.C., stood on the edge of the frontier at the Atlantic fall line, where the Upper Coastal Plain meets the foothills and plateau of the Piedmont.

Much of the surrounding countryside was developed by slave labor for cotton plantations, which was the major commodity crop of the South.

Cotton bales regularly were set up to line the roads, waiting to be shipped downriver to Darien.

Public-spirited citizens such as Mayor Tomlinson Fort (1847–1848) promoted better newspapers, learning academies, and banks.

(The college, forced to close in 1862 during the war, was rechartered in Atlanta in 1913) The cotton boom in this upland area significantly increased the demand for slave labor.

The town market, where slave auctions took place, was located on Capital Square, next to the Presbyterian church.

Skilled black carpenters, masons, and laborers were forced to construct most of the handsome antebellum structures in Milledgeville.

[8] Two events epitomized Milledgeville's status as the political and social center of Georgia in this period: By 1854 Baldwin County had a total population of 8,148, of whom 3,566 were free (mostly white), and 4,602 were African American slaves.

In part because of these institutions, as well as Central State Hospital, Milledgeville developed as a less provincial town than many of its neighbors.

In 1952 the Georgia Power Company completed a dam at Furman Shoals on the Oconee River, about 5 miles (8 km) north of town, creating a huge reservoir called Lake Sinclair.

It encouraged restoration of historic buildings and an urban design scheme on Main Street to emphasize its character.

Milledgeville is composed of two main districts: a heavily commercialized area along the highway known to locals simply as "441," extending from a few blocks north of Georgia College & State University to 4 miles (6 km) north of Milledgeville, and the "Downtown" area, encompassing the college, buildings housing city government agencies, various bars and restaurants.

In the November 2017 general election, incumbent Mayor Gary Thrower was defeated by Mary Parham-Copelan.