In 1861 the Civil War began and Slough immediately began recruiting for the federal army. Colorado Governor William Gilpin (governor) appointed him in the call for volunteers as a captain, the 1st Colorado "Pike's Peakers" Infantry Regiment. Members of his regiment were initially skeptical of his loyalty to the Union due to his association with the Democratic Party. In August 1861, Slough was commissioned colonel in command of the regiment. In 1862 a Confederate army was invading the New Mexico Territory, had defeated Col. Edward R. S. Canby's troops at the battle of Valverde, and captured Albuquerque and the capital of Santa Fe. Coming to the aid of the Union forces in New Mexico, Slough marched his regiment to Fort Union and, as the senior ranking officer, assumed command of the post, and its New Mexico Volunteers.