This Regiment was mustered in 16 September 1861 at St. Albans, Vermont, went to Meridian Hill at Washington, DC, then crossed Chain Bridge into Virginia and joined other Vermont Regiments at Camp Advance.

 The Regiment spent most of the fall and winter of 1861-62 at Camp Griffin, near Langley, Virginia, going to Fortress Monroe, Virginia in the spring of 1862 and taking part in the Peninsula Campaign. At Savage's Station, Virginia 29 June 1862 it suffered the greatest loss in killed and wounded of any Vermont Regiment in any single engagement, losing 188 officers and men in half an hour. It was here that five Cummings brothers, and one cousin, of Company E, were all killed or wounded, only one of the six recovering from his wounds.

 Returning in August, the Regiment marched across Cub Run, near the second Bull Run, Virginia battlefield. Subsequently it joined in the Maryland Campaign, then returned to Virginia, where it encamped during the winter of 1862-63 near Fredericksburg, taking part in the campaign near there in 1863, also skirmishing in the Pennsylvania Gettysburg Campaign.

 From Gettysburg it went into Virginia, then to New York City to help quell the draft riots. Returning to the Army of the Potomac it took part in the fall campaign in Virginia. It encamped during the winter of 1863-64 near Brandy Station, Virginia where it re-enlisted 15 December 1863, being the first Regiment to re-enlist and be allowed to travel home on a veteran furlough.

 In 1864 it took an active part in the ghastly campaign from the Rapidan to Petersburg Virginia, reaching the line in front of Petersburg 17 June. It went into this campaign with approximately five hundred muskets, and in one month lost 349 men in killed, wounded and missing, including two field officers, six captains and five lieutenants.

In July the Regiment returned and assisted in driving Confederate General Jubal Early from Washington DC, following him into the valley and becoming a part of the Army of the Shenandoah.

On 15 September 1864, the term of the original members of the Regiment who had not re-enlisted expired, and they were mustered out at Clifton, Virginia, leaving present for duty with the Regiment one assistant surgeon, a quartermaster, three first lieutenants and about three hundred men. This reduced Regiment participated in General Sheridan's campaign in the Shenandoah Valley, from Winchester to Mount Crawford, Virginia and back.

On 9 December the Regiment left the valley and returned to Petersburg, Virginia going into winter quarters 13 December near the Squirrel Level Road, south of Petersburg. It led the Sixth Corps in its assault upon the enemy's works at Petersburg on 2 April 1865, and was the first Regiment in the Corps to plant its flag upon the enemy's works. It took part in the pursuit and capture of General R. E. Lee's army, and after his surrender it marched to Danville, Virginia, to aid in preventing the escape of the army of Confederate General Johnston.

The Regiment then went to Munson's Hill, near Washington DC, where it was mustered out of the service of the United States 29 June 1865, and returned to Vermont to be finally discharged. When mustered out only 24 officers and 288 men remained upon its rolls, only 312 out of a total enrollment of 1,618 during its entire term of service.

During its four years of service the Regiment took an active part in the battles of Lee's Mills, Williamsburg, Golding's Farm, Savage's Station, White Oak Swamp, South Mountain, Antietam, Fredericksburg, Salem Heights, Gettysburg, Funkstown, Rappahannock Station, The Wilderness, Spotsylvania, Bloody Angle, Anderson's Farm, Jericho Ford, Cold Harbor, Petersburg, Fort Stevens, Charlestown, Winchester, Fisher's Hill, Cedar Creek, Petersburg, Sailor's Creek, and innumerable other skirmishes and reconnaissance’s.