The brigade suffered its most severe casualties in December at the
Battle of Fredericksburg where its fighting force was reduced from over 1600 to 256. The brigade was involved in the northern battleground at Fredericksburg where they assaulted the sunken road in front of Marye's Heights. Coincidentally, one of the regiments manning the sunken road defenses was a predominantly Irish Regiment commanded by Brigadier General
Thomas Reade Rootes Cobb. Knowing that Cobb's men manned the wall, and that both Cobb's and Meagher's units contained members of the
Irish Republican Brotherhood, an organization dedicated to gaining military experience in the United States, then freeing Ireland from Britain after the Civil War, Lee ordered reserves sent to the position. He need not have worried. Cobb's men helped decimate the Irish Brigade before the reinforcements could settle in place. It was at Fredericksburg that Lee allegedly referred to Meagher's regiment as the "Fighting 69th".
After the Battle of Fredericksburg, Gen. Meagher again requested to recruit the brigade back to strength. This time the request was denied. In May 1863, the brigade sustained further casualties at the
Battle of Chancellorsville, Meagher repeated his request to recruit replacements, was denied, and resigned his commission in protest. Meagher was replaced by Colonel
Patrick Kelly.
Leading up to the Battle of Gettysburg, the brigade recovered several hundred of its injured from Fredericksburg and was able to field nearly 600 men - in reality, barely at regimental size. At Gettysburg, the brigade distinguished itself in the Wheatfield under the command of Col. Kelly as the 2nd Brigade of the 1st Division