Composed mainly of Worcester county men. It left the State August 23, 1861, and was stationed at Annapolis until January 6, 1862, when it sailed with the Burnside expedition to North Carolina, having been brigaded in General Reno's command. Under command of Lieutenant-Colonel Alberto C. Maggi, it was prominently engaged at Roanoke Island, where its casualties were 5 killed and 39 wounded. In the following month, commanded by Colonel Clarke, it fought gallantly at New Berne, where it suffered a loss of 15 killed and 42 wounded; among the killed was Adjutant Stearns. At Chantilly--in Ferrero's Brigade, Reno's Division--the regiment encountered the hardest fighting in its experience; Lieutenant-Colonel Joseph P. Rice was killed, and the total of casualties amounted to 22 killed, 98 wounded, and 26 captured, out of less than 400 men present in action. At Fredericksburg-- Ferrero's (2d) Brigade, Sturgis's (2d) Division -- the regiment rendered efficient service by the skill with which, from an advanced position and good marksmanship, it kept down the enemy's fire. In this action two color bearers were killed, and others were wounded, one of the latter losing both arms. Leasure's Brigade distinguished itself particularly in the battle of the Wilderness, where it swept down the line, across and opposite Hancock's front; it was a daring charge, and accomplished with a remarkably small loss. The Twenty-first was mustered out in October, 1864; the men remaining in the field were transferred to the Thirty-sixth Massachusetts.