Struble fought in the Civil War. In August 1862, Struble (then 18) enlisted in Company F of the 22nd Iowa Volunteer Infantry Regiment, marching in the ranks of the Union Army as a private. When he first donned the uniform of the Union, Isaac stood 5'8" with brown eyes and reddish hair. After he was wounded in the Battle of Cedar Creek in Virginia on October 19, 1864, he was promoted to the rank of sergeant. He was mustered out of the service on July 25, 1865. In addition to Cedar Creek, his combat experience included the Battle of Port Gibson, the Siege of Vicksburg, and the Battle of Opequon (otherwise known as the Third Battle of Winchester).