Greenup is a home rule-class city in and the county seat of Greenup County, Kentucky, United States, located at the confluence of the Little Sandy River with the Ohio River.

Greenup was laid out in 1803 and 1804 by Robert Johnson, a pioneer and legislator who owned the land.

Upon the formation of Greenup County (named for the former congressman Christopher Greenup, who later served as governor) out of land separated from Mason County, Johnson's settlement was chosen to be the seat of government and adopted the name "Greenupsburg".

The name was shortened to "Greenup" on March 13, 1872, partially to avoid confusion with Greensburg.

[7] Some people left the area permanently, with the population of Greenup showing a decline of 5.5% in the 1940 census.

U.S. Route 23 (Seaton Avenue) runs through the southwest side of the city, leading northwest 19 miles (31 km) to Portsmouth, Ohio and southeast 13 miles (21 km) to Ashland, Kentucky.

Its representative body is the city council, which has six members elected from single-member districts.

In addition, surrounding fire and police departments are in a mutual aid agreement with the city of Greenup.