On March 25, 1822, state officials decided to build a new county seat named "Liberty", 1.5 miles (2.4 km) below the mouth of the Russell Fork.

led a new decision on December 24, 1823, to establish the county seat on land donated by local farmer Elijah Adkins.

Pikeville was host to part of the Hatfield-McCoy feud, and patriarch Randall McCoy as well as his wife and daughter are buried on a hillside overlooking the town.

[10] The project alleviated traffic congestion in downtown and eliminated flooding by rerouting the Levisa Fork River.

Baseball Hall of Fame member Greg Maddux played for the 1984 Pikeville Cubs in his first professional season.

[16] Late 2017 saw several announcements regarding tenants for the recently opened Kentucky Enterprise Industrial Park.

The city is in the Appalachian Mountains, along the Levisa Fork of the Big Sandy River.

The downtown area is built in a narrow valley in a bend of the Levisa Fork that was bypassed in 1987 with the completion of the Pikeville Cut-Through, while places such as Weddington Square Plaza are built in a broader part of the river valley.

The racial makeup of the city was 93.8% White, 2.9% Black, 0.5% Native American, 1.3% Asian alone, 0.0% Pacific Islander, 1.5% from two or more races, and 2.2% Hispanic or Latino.

Hillbilly Days is an annual festival held in mid-April in Pikeville, celebrating Appalachian culture.

The festival honors and recognizes the heritage of Appalachia, while poking fun at the stereotype associated with the region.

In 2005, the Appalachian Wireless Arena, formerly known as the Eastern Kentucky Expo Center, opened in downtown Pikeville.

The center, which seats 7,000, features numerous events including concerts and shows.

The city is also home to the Pikeville Concert Association, which secures cultural events for the area.

The Appalachian Center for the Arts is a 200-seat indoor professional theater in downtown Pikeville.

[25] The name was inspired by the Hatfield-McCoy Feud, and the tour includes storytellers describing those events in addition to an explanation of the brewing and distilling processes.