The regiment mustered into service in May 1862 and was captured at the Battle of Harper's Ferry.

After being paroled and exchanged, the regiment was sent to Kentucky and assigned to the XXIII Corps.

After being paroled, the regiment was moved to Kentucky as part of the XXIII Corps and participated in the November–December 1863 Siege of Knoxville.

When the Confederates under General John Hood headed north into Tennessee late in the year, the 65th was part of Col. John S. Casement's brigade, James W. Reilly's 3rd Division sent after him, joining in the battles at Franklin and Nashville.

This article about a specific military unit of the American Civil War is a stub.