The regimental commander, Col. Charles J. Williams, died on February 8, 1862.

Now led by Col. William J. Magill, the regiment served in the Army of Northern Virginia in the Eastern Theater of the American Civil War.

In Gen. George P. Harrison's brigade it participated in the Battle of Olustee.

When Magill retired on September 3, 1864, Wayne was named as his successor.

The regiment was surrendered along with Joseph E. Johnston's army at Bennett Place in North Carolina on April 26, 1865.