Commanded by Colonel Walter Q. Gresham, a lawyer who had been born on 17 March 1832 and had enlisted as a Lieutenant Colonel at the age of 29 on August 27, 1861. Gresham was commissioned in Company S, 38th Infantry Regiment Indiana in mid-September 1861 and by February of the following year, had been promoted to Full Colonel of the 53rd Indiana Infantry.

Field and Staff of the 53rd consisted of Major and Lieutenant Colonel Henry Duncan; Lieutenant Colonel Andrew H. Fabrique; and Captain William W. Curry, all of New Albany. Company B's commissioned officers included Captain and 1st Lieutenant A.H. Fabrique; and 1st Lieutenant John M. Austin, both of New Albany; and non-commissioned officer Corporal John M. Austin. Captain of Company D was Seth Daily of Charlestown; Captain and 2nd Lieutenant William Howard of Jeffersonville; 1st & 2nd Lieutenant John L. Gibson of New Albany; and 1st Lieutenant James Engleman of Georgetown.

The regiment's first movement was to Indianapolis. There it guarded rebel prisoners at Camp Morton where the first group of prisoners had arrived on the 22nd of February and within the three days would total 3,700. It had been converted to hold the rebel prisoners after the fall of Fort Henry and Fort Donelson, and was erected under the command of Captain James A. Ekin who was an assistant quartermaster general of the United States Army.

The regiment remained here until March 15th, after which time it headed for St. Louis and on to Savannah, Tennessee. They joined the forces headed toward Corinth on April 15th, and after its evacuation, it marched to Lagrange and joined the expeditions from there to Holly Springs.

After being at Memphis in September, followed by Bolivar, they moved again on Corinth and on October 5th, participated in the battle at Hatchie Bridge, Tennessee where U.S. General Rosecrans was to pursue the Confederate forces and trap them on the east side of the Hatchie River. Although Rosecrans failed to move quickly enough, the 53rd had courageously crossed the burning Davis Bridge and charged the Rebel line.

While the Union navy prevented other regiments from joining Confederate General C. Pemberton at Vicksburg, Grant moved forward with a direct assault to attack the city. The fighting raged on for a six-week siege which had sent the residents of Vicksburg literally underground. They escaped from their homes and dug caves in the sides of the bluffs, so many that it was come to be known as "Prairie Dog Village.:

Starving but hopeful, the soldiers and civilians endured the sufferings until it was evident to General Pemberton that his troops were exhausted, over-powered, and worn down with fatigue. Sending a note to Grant under a flag of truce on July 3rd, the two generals met while hundreds of soldiers lay silently watching from atop the earthworks.

The 53rd had taken an honorable part in the battle of Vicksburg which had lasted forty eight days and in which an excess of 19,000 soldiers had lost their lives. Vicksburg had surrendered, the Confederacy was now split in half, and the Union had gained control of the Mississippi River - but the war raged on.

Intending to cut the city of Jackson, Mississippi and the railroad off from Vicksburg, the Union Army of Tennessee advanced on the city, burned part of the town and were successful in cutting the railroad connections to Vicksburg. Had Confederate General Joseph E. Johnston been able to overcome the Union forces, he would have had an additional 15,000 troops at his disposal within the week.

While the Confederates suffered a sincere blow to their morale, the regiment left Jackson on the 16th of July and returned to Vicksburg. The regiment served reconnaissance to Pearl River and duty at Vicksburg until August 15th when it was ordered to Natchez, Mississippi, and quartered there for about three months during which time Colonel Gresham was commissioned brigadier. Lieutenant Colonel Jones succeeded as regimental commander of the regiment was attached to the 17th corps and would then join the expedition into Louisiana.

The regiment returned to Vicksburg where it remained until February of 1864, and then joined in the Meridian campaign. At Hebron Mississippi., three hundred and eight-three of the regiment re-enlisted and were furloughed home in March. They joined Sherman's army at Acworth, Georgia on June 6th, 1864, and participated in most of the battles and skirmishes of the Atlanta campaign, being engaged at Kennesaw Mountain and Peachtree Creek as was the 22nd Indiana regiment.

After Sherman surrounded Atlanta and Confederate General John Bell Hood evacuated the city, the south was cut off from obtaining supplies from farm or factory. Grant was then able to force Lee, who was commanding the Army of Northern Virginia, out of Petersburg and Richmond and a surrender was accepted at Appomattox Court House, Virginia.

The regiment had joined the pursuit of General Hood after the fall of Atlanta and took part in the advance on Savannah to ravage South Carolina and hunt down the last of the Southern resistance in the mountains of North Carolina where Johnston surrendered on 26 April 1865.

The regiment then went to Washington, D. C., thence to Louisville, and was there mustered out July 21, 1865. It returned to Indianapolis and was in the public reception on July 25th where they were soon after discharged. The war was over, but the regiment, had lost nine officers and ninety-eight enlisted men killed and mortally wounded; and four officers and 248 enlisted men by disease, for a total of 359.

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