The 16th Infantry Illinois Volunteers was organized and mustered into United States service at Quincy, Illinois 24 May 1861, and on 12 June moved to Grand River. On 10 July it was attacked at Monroe Station by 1,600 mounted Rebels, but held its position until the arrival of reinforcements, when the enemy retired. Six days later the Regiment lost two men killed and two wounded at Caldwell Station. On 20 August the Regiment moved to Kirksville in pursuit of General Green, arrived at Hannywell on 1 September, went to St. Joseph, Missouri on the 10^th, four days later with the Third Iowa Infantry, skirmished at Platte City, returning to St. Joseph 17 September.

During the year 1862 the Regiment was engaged in combat and/or pursued the enemy at New Madrid, Tiptonville, Corinth, Booneville, Big Springs, Tuscumbia, Florence, Nashville, and Edgefield, Tennessee. While at Edgefield they were attacked by Rebel General Morgan, who was repulsed, leaving many dead upon the field, while the Regiment lost only one killed and five wounded.  The Regiment remained in garrison duty at Edgefield until the middle of July 1863 when it broke camp and marched to Murfreesboro, then to Columbia, Tennessee, and on to Athens, Huntsville and Stevenson, Alabama. A few days later it made a forced march to Bridgeport where, while guarding ordnance stores and a pontoon bridge, an immense quantity of nearby ordnance exploded resulting in 14 killed and wounded.

Early in October a 40 mile march was made up the Sequatchie Valley to Anderson's Gap where the Regiment was transferred from the First Brigade, First Division, Reserve Corps of the Army of the Cumberland to the First Brigade, Second Division, 14th Army Corps. From Anderson's Gap the Regiment marched to Waldross Ridge, then to Kelly's Ferry where it was occupied through December 1863 unloading the rations, forage and ammunition from boats to be sent forward to Thomas' Army at Chattanooga.

After the Regiment re-enlisted as Veterans they left on 1 January 1864 for Illinois on a 30-day furlough. After the furlough the Regiment redeployed with Sherman's Army on the Atlanta campaign and later was in advance at Buzzard Roost where the Regiment suffered 18 killed and wounded.

The Regiment marched through Snake Creek Gap, fought the battle of Resaca and flanked the rebels from Dalton, then moved on to help capture Rome, Georgia, then on to Lost Mountain, Kennesaw Mountain, and was the first unit to cross the Chattahoochee River. It participated in the battle of Peach Tree Creek, losing a number by wounds and prisoners by marching into the line of the enemy while the Regiment was making a night advance to the front.

The Regiment later held a position on the front line at Atlanta and for thirty days was constantly engaged in skirmish firing. In August it withdrew from the front, swung around the city to the west, and on 30 August while in the battle at Jonesboro where the enemy's line was broken and Atlanta was won, the 16th had charged with fixed bayonets and empty guns, and helped carry the battle.

 After the capture of Atlanta the Regiment was sent with the Division back to Chattanooga, Huntsville and Athens, then returned to Atlanta. The Corps was taken from the Army of the Cumberland and with the 12th Corps, becoming the Army of Georgia, which made Sherman's march to the sea. Later it had the honor of being the representative Regiment of the 14th Army Corps to take formal possession of Savannah, Georgia. They marched north through the Carolinas during February and March, 1865; assisted in the capture of Columbia and Fayetteville; and participated in the Battle of Averysboro, where the Regiment lost 15 or 20 killed and wounded.

The March 1865 battle of Bentonville the 16th on the front line saw Rebels drive the supporting Regiments from their works and into the swamp. Having repelled the assault in front the 16th, with the assistance of the 14th Michigan, charged the rebel line, capturing some 800. The second day of the battle the 16th and the 14th Michigan, through a blunder of the Colonel of the Michigan unit, charged into the center of the rebel forces resulting in the loss to Company A of ten men, seven of whom died on the field, or soon thereafter.

After this battle the 16th moved to Goldsboro, Raleigh and Durham Station where General Johnson surrendered his Army to General Sherman. They marched with Sherman's Army to Richmond and participated in the Grand Review in Washington on 24 May 1865.

The Regiment proceeded to Louisville, Kentucky, then to Springfield, Illinois, where it received its final pay and discharge papers.

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