Maj. Gen. Geirge Sykes, Commander, 2nd Division, V Corps. The 11th U.S. Infantry would serve most of its time in combat under General Sykes.
Brig. Gen. Romeyn B. Ayres. Ayres took over the 2nd Division when Sykes assumed command of the V Corps in late June 1863.
Col. Montgomery C. Meigs served as the commander of the 11th U.S. Infantry for one day. He was appointed Quartermaster General of the U.S. Army on 15 May 1861.
Col. Erasmus D. Keyes assumed command of the 11th U.S. Infantry on 15 May 1861, but left the regiment at Boston, MA, on 3 July 1861 when he was appointed commander of the IV Corps.
Maj. Charles S. Lovell commanded the the 2nd Brigade, 2nd Division during the Peninsula Campaign until after Gaines Mill.
Col. William Chapman, led the 2nd Brigade, Sykes Division through the battles of Malvern Hill and Second Bull Run
Col. Sidney Burbank commanded the 2nd Brigade, 2nd Division at Chancellorsville and Gettysburg.
Lt. Col. Edmund Shriver led the regiment through its train up at Fort Independence and Perryville, July 1861 to March 1862.
Maj. Delancey Floyd-Jones, 1st Battalion commander, would lead the 11th U.S. Infantry through all its major battles in 1862 and 1863 except Fredericksburg.
Major Jonathan W. Gordan spent most of his time with the regiment as the Superintendent of the Regimental Recruiting Service and the Recruit Depot at Fort Independence. He would only see action in command of the regiment at Mine Run in December 1863.
Though assigned as second in command of the 11th U.S. Infantry in March 1863, Lt. Col. John T. Sprague would serve only 2 weeks with the regiment in February 1865 at City Point, VA.
Maj. Daniel Huston, Jr. commanded the regiment for the last 2 months of the Civil War.