On November 10, 1861, a Confederate cavalry force of more than 700 attacked a Union recruit camp for the Ninth (West) Virginia Infantry regiment at Guyandotte in Cabell County. Led by Col. John Clarkson, the Confederates quickly overcame the brief but spirited resistance of the federal recruits, who numbered slightly more than 100 men. The night was a joyful one for many of Guyandotte's citizens, a majority of whom had been outspoken advocates of secession. Ninety-eight Union recruits and civilians from the town were captured and on the following day forced to begin a harrowing march to imprisonment in Richmond.

On the morning of November 11, as the Confederates were withdrawing from Guyandotte, a detachment of the Fifth (West) Virginia arrived from Ceredo on the steamer S.S. Boston. Accompanied by a number of Home Guards from Ohio, the Union troops burned a large portion of the town in response to accusations that the townspeople had aided the Confederates in planning and carrying out their attack. Probably a more important factor in the decision to burn the town, however, was Guyandotte's reputation as a hotbed of secession. Northern newspapers expressed outrage over the actions of the town's citizens and rejoiced at Guyandotte's destruction. Shortly after the raid, the Wheeling Daily Intelligencer wrote that due to the town's outspoken advocation of secession, Guyandotte "ought to have been burned two or three years ago."