During the American Civil War, Collins was appointed colonel of the 7th Ohio Cavalry. However, this regiment never completed its muster and was therefore consolidated with the 6th Ohio Cavalry. Collins was now named lieutenant colonel of the 6th Ohio Cavalry with William Lloyd as colonel. Collins was resentful his regiment had been absorbed into another and used his political influence to have his original four companies transferred to an independent command. Ordered to St. Louis MO in February 1862, Collins' command was officially declared the 1st Ohio Independent Cavalry Battalion. Collins served under General James Craig protecting the Overland Mail routes in Nebraska Territory. In June 1862, four additional companies were recruited at Camp Dennison to be added to the 1st Ohio Cavalry Battilion. Before Collins could unite the two battalions, the new recruits were mobilized for the defense against Morgan's Ohio Raid. Also during this time General Craig ordered troops to establish a military post in northern Colorado Territory. Craig named the post Camp Collins in honor of the Ohio cavalry officer. The two Ohio cavalry battalions were joined to create the 11th Ohio Cavalry and on September 20, 1862 Collins was appointed lieutenant colonel, the "de facto" commanding officer. Lieutenant Colonel Collins commanded Fort Laramie from 1863–1864. In August, he authorized the establishment of "Fort" Collins the previous establishment having been destroyed by a flood. Collins commanded the Western Sub-district of the District of Nebraska from 1864–1865. During this time he led troops into action against Native American warriors in the battles of Mud Springs and Rush Creek. In April 1865, Collins and the original four companies of the 11th Ohio Cavalry were mustered out of the volunteer service.