Mustering on April 17, 1861, under Colonel Alexander M. McCook, the 1st Ohio Infantry Regiment travelled by train to Washington, D.C. for garrison duty in the capital's fortifications and defenses until July.

[1] After the term of service was over in August, a number of the men re-enlisted for 3-years in the reconstituted 1st Ohio Infantry Regiment, under the command of Col. Benjamin F. Smith.

[2] In late winter 1862 the regiment was attached to the 4th Brigade, 2nd Division, Army of the Ohio, serving in Tennessee under Don Carlos Buell at Shiloh.

Following Shiloh, the regiment served in Mississippi during the Siege of Corinth before moving to Tuscumbi, Florence, and Huntsville Alabama, June 10 - July 5.

In August, the regiment returned to Kentucky (Louisville) as the army pursued Confederates under Braxton Bragg, fighting at the Battle of Perryville.

A number of recruits re-enlisted and transferred to the 18th Ohio Volunteer Infantry on October 31, 1864, and remained on duty through the end of the Civil War.

The tattered battle flags of both the three-months and three-years regiments (as well as the guidon of Company B, the Lafayette Guards) are preserved in the museum of the Ohio Historical Society in Columbus.