The 88th Ohio Infantry was organized at Camp Chase in Columbus, Ohio, in July 1862 and mustered in on October 27, 1862, for three years service under Colonel George Washington Neff.

When Edmund Kirby Smith threatened Cincinnati, Ohio, in September 1862, the 88th moved to Covington, Kentucky, but soon returned to Camp Chase.

A detachment then served in western Virginia and Maryland, but returned to Ohio to operate against John Hunt Morgan.

It then returned to Columbus to serve guard duty at Camp Chase until July 1865.

The regiment lost a total of 80 enlisted men, all due to disease.