Okolona was just coming into its own when the Civil War began. Because of the railroad, the town was strategically important. As a result, skirmishes between Union and Confederate forces occurred at or near Okolona at least five times, beginning in November, 1862. In February, 1864, Federal forces under Brigadier General William Sooy Smith entered Okolona during his move from Memphis in cooperation with Major General William T. Sherman's Meridian Expedition. On February 22, Smith's forces, retreating from West Point, were defeated by Confederate cavalry under Major General Nathan Bedford Forrest north and west of town. In a running battle which culminated in the action at Ivey's Hill, believed to be approximately ten miles north of Okolona on the Pontotoc Road, the Federals were pushed back to Memphis. During the afternoon of the 22nd, general Forrest's younger brother Jeffrey, in command of a cavalry brigade, was killed. A number of houses and public buildings in Okolona were subsequently used as hospital sites. Hospitals were established at Okolona at other times during the war, most notably as a result of the battles of Shiloh and Corinth.