The largest battle in eastern Kentucky, the Battle of Middle Creek, was fought on the high ridges near Prestonsburg on January 10, 1862.  Both sides were evenly matched in this engagement, with forces of about 1500 each.  The Confederates were commanded by General Humphrey Marshall, and the Union troops by future President James A. Garfield, who was promoted to Brigadier General after his performance in the battle.  Although victory was claimed by both sides after light casualties, a late-night retreat by the Confederate forces left the Union army in control of eastern Kentucky.

A re-enactment of the Battle of Middle Creek is held annually.