The regiment was mustered into service in August of 1862. It was stationed at Harper's Ferry, Virginia during the Antietam Campaign. When the town was surrounded by the Confederate Army, the regiment surrendered. After the release of the soldiers, the 115th served in the Defense of Washington, and in December of 1863 the regiment was transferred to the Florida Expedition where they fought the Battle of Olustee.
In 1864, the regiment participated in the campaign against Richmond and Petersburg, and it appears that the 115th participated in many other engagements and battles of the war.