On April 12, 1861, Confederate forces that had recently seceded from the Union fired upon Federal controlled Fort Sumter in Charleston, South Carolina.
Among the early recruits in Company F was Fremont dentist Everton Conger, who later in the war led the cavalry that tracked down and killed President Abraham Lincoln's assassin, John Wilkes Booth.
While in the Shenandoah Valley, the regiment participated in its first real battle, Kernstown, where it attacked and defeated a portion of Stonewall Jackson's force, while suffering almost twenty-five percent casualties.
In September 1862, during the Maryland Campaign, the regiment and the rest of the II Corps hastily marched northward in pursuit of Robert E. Lee's Army of Northern Virginia.
Kimball's brigade repeatedly attacked Alabama troops under D. H. Hill stationed in a sunken road during the Battle of Antietam, taking 50% casualties but eventually pushing through the defensive line at a cost of 162 officers and men killed or wounded.
[4] In early December, replenished by new recruits, the 8th Ohio participated in the Battle of Fredericksburg, where it was initially assigned as skirmishers after crossing the Rappahannock River on pontoon bridges.
From the comparative safety of their position, the men witnessed the series of bloody and futile attacks on Marye's Heights ordered by Ambrose Burnside.
In response, the Union army, first under Joseph Hooker and then under George G. Meade, slowly began to pursue Lee into Maryland and subsequently into south-central Pennsylvania.
Facing a force several times its number, the 8th Ohio held its advanced position and was able to flank portions of a Virginia brigade under Col. John M. Brockenbrough.
Assisted by artillery fire from Cemetery Hill and Ziegler's Grove, the 8th succeeded in routing much of Brockenbrough's force, the first brigade to ever break and flee during Lee's tenure in command of the Army of Northern Virginia.
After fighting at the Battle of Spotsylvania Court House, the 8th marched southward as Ulysses S. Grant continually sidestepped Lee and relentlessly moved towards Richmond and Petersburg.
With only three weeks left in their original three-year term of enlistment, on June 1 the regiment was sent forward in the ill-fated attacks at the Battle of Cold Harbor, where it again suffered considerable casualties before withdrawing.