[1] The various companies of what would become the 21st Mississippi were raised independently in May–August 1861 and travelled to Manassas, Virginia, where they were organized into a regiment in October of that year.

In 1863, the regiment was part of the Chancellorsville campaign, during which it held a sparsely-defended position at the stone wall of Marye's Heights in the face of heavy opposition.

[2] At Gettysburg, the 21st regiment was involved in heavy fighting, during which the brigade commander General Barksdale was mortally wounded.

After the retreat from Gettysburg, Colonel Benjamin G. Humphreys of the 21st was promoted to brigadier general and the regiment was moved south to Georgia, where they fought at the Battle of Chickamauga.

[2] The 21st, which by that point only consisted of 4 officers and 44 men,[3] then surrendered with Robert E. Lee's forces at Appomattox on April 9, 1865.