On the return of the 20th New York State Militia Regiment from its three months' service, Col. George W. Pratt reorganized it at Kingston, New York, as a regiment of volunteers, and it was mustered in the service of the United States for three years between September 20 and October 20, 1861.

The regiment left for Washington, D.C., and performed picket duty along the Potomac in the vicinity of Upton's Hill, during the first winter.

It was active at South mountain and Antietam, encamped at Sharpsburg for one week and marched through Crampton's Gap, Leesburg, Warrenton and Stafford Court House to Fredericksburg, where it participated in the battle.

After the battle of Gettysburg, the 80th was again ordered to headquarters for provost guard duty and continued in this service until the end of the siege of Petersburg, when it shared in the final assault, April 2, 1865.

From April 22 to November 27, 1865, it was stationed at Richmond and then ordered to Norfolk, where it remained until mustered out on January 29, 1866.