The 81st New York Infantry was organized at Albany, New York beginning February 18, 1862, and mustered on December 20, 1861, through February 20, 1862, for a three-year enlistment under the command of Colonel Edwin Rose.

The regiment was attached to the 3rd Brigade, 3rd Division, IV Corps, Army of the Potomac, to June 1862.

1st Brigade, 2nd Division, XVIII Corps, Department of North Carolina, to February 1863.

1st Brigade, 1st Division, XVIII Corps, Department of the South, to April 1863.

District of Beaufort, North Carolina, XVIII Corps, to October 1863.

District of the Currituck, Department of Virginia and North Carolina, to March 1864.

1st Brigade, Heckman's Division, Department of Virginia and North Carolina, to April 1864.

1st Brigade, 1st Division, XVIII Corps, Army of the James, to December 1864.

District of Beaufort, NC, 18th Army Corps, to October 1863.

Duty at Kalorama Heights, Defenses of Washington, DC, March 7–13, 1862.

The movement to Fortress Monroe August 16–22, and duty there until September 18.

Moved to Newport News, VA, October 16–18, and duty there until January 1864.

They moved to Portsmouth, VA, on January 22, and duty there and in the District of the Currituck until April 1864.

Butler's operations on the south side of the James River and against Petersburg and Richmond May 4–28.

Siege operations against Petersburg and Richmond from June 16, 1864, to April 2, 1865.

Battle of Chaffin's Farm, New Market Heights, September 28–30.