The First Texas Infantry was organized in Virginia in August 1861 after ten companies, lettered A to K, that arrived from Texas were consolidated into a regiment. Two additional companies, lettered L and M, were later added to the regiment, bringing the total to twelve. Men serving in the regiment came from the Texas counties of Anderson, Cass, Cherokee, Galveston, Harrison, Houston, Marion, Nacogdoches, Newton, Polk, Sabine, San Augustine, Trinity, and Tyler. The regiment's original commander was Col. Louis T. Wigfall who received a promotion to brigadier general on October 21, 1861. Wigfall's military service was brief; on February 20, 1862, he resigned to take his seat in the Confederate Congress in Richmond, Virginia. Field officers for the regiment at its mustering in were Maj. Frederick S. Bass, Maj. Harvey H. Black, Maj. Albert G. Clopton, Maj. Matt Dale, Maj. Richard J. Harding, Maj. Hugh McLeod, Maj. Alexis T. Rainey, Maj. John R. Woodward, and Lt. Col. Phillip A. Work.

This regiment was one of three from Texas that became part of Hood's Texas Brigade commanded by Gen. John Bell Hood. The First Texas Infantry was first assigned to duty in the Potomac District and became part of the Army of Northern Virginia. Attached to the Corps commanded by Gen. James Longstreet, the regiment saw extensive combat throughout the war and served primarily in Georgia, Tennessee, and Virginia. Under Longstreet's command the regiment served in Georgia in September 1863, then went to Tennessee, and came back to Virginia in the spring of 1864 where it remained to war's end.

The First Texas Infantry participated in a long and impressive list of military engagements, including thirty-two major battles. Their largest engagements included Seven Pines from May 31 to June 1, 1862; the Seven Days Battles from June 25 to July 1, 1862; Second Bull Run on August 28–30, 1862; Antietam on September 17, 1862; Fredericksburg on December 13, 1862; Gettysburg on July 1–3, 1863; Chickamauga on September 19–20, 1863; the siege of Chattanooga from September to November 1863; the Wilderness on May 5–6, 1864; Spotsylvania Court House from May 8 to 21, 1864; Cold Harbor on June 1–3, 1864; and the Petersburg siege from June 1864 to April 1865.

The regiment surrendered along with the rest of the Army of Northern Virginia at Appomattox Court House on April 9, 1865.Throughout the war the First Texas Infantry suffered heavy casualties. At the battle of Antietam the regiment lost 82 percent of its 226 troops engaged. More than 20 percent of its 426 troops were lost at the battle of Gettysburg. At the time of its surrender at Appomattox Court House the regiment had only 16 officers and 133 men. All of the men who surrendered at Appomattox Court House were paroled by the Union Army under Ulysses S. Grant and allowed to return home.