On December 13, 1861, Peirce joined the volunteer forces as colonel of the 29th Massachusetts Infantry Regiment. His regiment was located at Fort Monroe and was involved in the battle of Hampton Roads. He was court-martialed for presenting burlesque shows to the troops of his command and for incompetency, but was acquitted. Peirce then fought in the Peninsula Campaign and the Seven Days Battles where, on June 30, 1862, he lost his right arm at the Battle of White Oak Swamp, considered part of the larger Battle of Glendale or Nelson's Farm. He was out of action until November 1862 when he returned to command his regiment and served in the siege of Knoxville. His regiment returned to Virginia with the rest of the IX Corps and fought at Cold Harbor. He commanded a brigade at the Second Battle of Petersburg. Peirce commanded a brigade during the following time periods: August 18–September 18, 1863; January 10–March 16, 1864; and, June 4–July 23, 1864. Peirce was discharged from the volunteer service on November 4, 1864 due to the loss of his right arm and general nervous debility relating to miasmatic diseases, and returned to Assonet. In 1880, he served one year as a member of the Freetown Board of Selectmen.