Col. George Flournoy organized the Sixteenth Texas Infantry Regiment into service of the Confederacy on March 25, 1862, at Camp Groce near Hempstead, Texas. Also known as George Flournoy's Infantry, the unit consisted of ten companies made up mainly of men from Central Texas, primarily Austin, Belton, and Washington counties. Colonel Flournoy, who remained with the regiment throughout the war, was attorney general for the state of Texas at the outbreak of the conflict. A major proponent of separating from the Union, he was one of the authors of the state's declaration of causes for secession. In 1862 he resigned his post as attorney general to form the Sixteenth. Flournoy was joined by Lt. Col. James E. Shepard, Maj. William H. Redwood, and Xenophon B. Saunders as field officers; U. G. M Walker as his surgeon; and R. L. Upshaw as his adjutant. The Sixteenth spent the entire war fighting on the Trans-Mississippi side of the Confederacy.
Initially assigned to the Eastern District of Texas, the Sixteenth Texas remained at Camp Groce until May 16, 1862, when it was ordered to proceed to Virginia Point, Texas. There, the regiment saw no action and was ordered to advance to Little Rock, Arkansas, where it spent the fall and winter at Camp Nelson. During this time, Brig.Gen. Henry McCulloch formed the Second Division, with the Sixteenth as a part of its Third Brigade. Although Colonel Flournoy took temporary command of this brigade, McCulloch replaced him when Maj. Gen. John G. Walker assumed overall command of the division. As part of Walker's Texas Division, the Sixteenth first saw action at Milliken's Bend. During the battle, the regiment nearly overtook a Union position, but General McCulloch ordered them to another area before they could complete the task. Still, the Sixteenth managed to capture some Federals, including a company of black soldiers. The unit had two men die and suffered five wounded during the battle.
In October 1863 the Sixteenth was sent to assist Gen. Thomas Green's forces in defending the town of Opelousas, Louisiana. There, Union forces quickly drove the regiment back and took possession of the town. The Sixteenth did not see any action the rest of the winter with the exception of firing on Union steamboats on the Mississippi. In April 1864 the Sixteenth proceeded to Mansfield, Louisiana, as part of the Red River campaign. On April 8, 1864, the regiment participated in a Confederate victory at Mansfield where they "did particularly effective work." The next day they fought Union forces in the battle of Pleasant Hill. At the end of the month, the Sixteenth proceeded to Grant County, Arkansas, where they arrived in time to fight the battle of Jenkins' Ferry on April 30, 1864. In total, Union forces captured three officers and thirty men of the Sixteenth during the Red River campaign.
The regiment saw no action for the rest of the war. During the winter of 1864, the Sixteenth took up residence near Minden, Arkansas, where the now "ragged and barefooted" group remained until January 26, 1865. From there they proceeded to Shreveport, Louisiana, where they were reassigned to the recently-created Fourth Brigade of Walker's Division. The Sixteenth was then ordered to proceed to Hempstead, Texas, where they had started the war. There, the unit unofficially disbanded on April 30, 1865. Gen. Edmund Kirby Smith officially surrendered the regiment in Galveston on May 26, 1865.
General Flournoy and some of the men of the Sixteenth fled to Mexico prior to the end of the war where they went on to serve for a time as a part of Maximilian's forces. Flournoy later returned to Texas where he practiced law and took part in the 1875 constitutional convention. Other notable members of the Sixteenth Texas Infantry included journalist Will Lambert, minister Robert Hay Taliaferro, state senator William Hamilton Ledbetter, and judges Zimri Hunt and Littleton Wilde Moore.