Serving in the forces under Ulysses S. Grant, the 1st Nebraska Infantry participated in the successful attack on Fort Donelson in Tennessee and then fought at the Battle of Shiloh in April 1862. It then participated in several minor engagements in Missouri and Arkansas. In October 1863, the regiment was changed from infantry into cavalry, and was transferred to the frontier to keep the Plains Indians in check. It was mustered out of the Union Army in 1866.