Col. Elkanah B. Greer mustered the Third Texas Cavalry Regiment into Confederate service at Dallas on June 13, 1861. The original unit consisted of 1,094 officers and men recruited principally from a dozen counties of Northeast Texas: Cass, Cherokee, Harrison, Hunt, Kaufman, Marion, Rusk, San Augustine, Shelby, Smith, Upshur, and Wood. With Lt. Col. Walter P. Lane as second in command, George W. Chilton as major, and Capt. Mathew D. Ector as adjutant, Greer led the ten companies north across Indian Territory to join Brig. Gen. Benjamin McCulloch's forces near Springfield in July 1861. The unit was the first regiment of Texas volunteers to serve outside the state. Greer's troops participated in the Confederate victories at Wilson's Creek, Missouri, on August 10, 1861, and Chustenahlah, Indian Territory, on December 26, 1861. They were present but not engaged on March 7–8, 1862, at Pea Ridge, Arkansas, where McCulloch lost his life. The unit, which had been consolidated with Sterling Price's command before Pea Ridge and absorbed into the army of Maj. Gen. Earl Van Dorn, was transferred to Corinth, Mississippi, in the spring of 1862. In the fever-ridden campgrounds around Corinth, forty-three troopers from the Third Texas died from the effects of epidemic disease. An additional 200 officers and men were discharged as disabled, over age, or under age in the course of the general reorganization of the Confederate Army on May 20, 1862. Nevertheless, the regiment played a significant role in Gen. Pierre G. T. Beauregard's successful evacuation of Corinth on the night of May 29–30, 1862.
The regiment, reorganized as part of Maj. Gen. Sterling Price's Army of the West, sustained its most severe one-day loss on September 19, 1862, when twenty-two men were killed, seventy-four wounded, and forty-eight captured in the battle of Iuka, Mississippi. Shortly thereafter, on October 3–4, the regiment participated in Van Dorn's costly and unsuccessful attack on the Union fortifications at Corinth. Two months later the Third Texas formed part of Van Dorn's cavalry column, which staged the spectacularly successful Holly Springs raid, thereby delaying Union major general Ulysses S. Grant's projected attack on Vicksburg by half a year. In February 1863 the troopers marched north into Tennessee to engage Union forces south of Nashville. There they participated in the Confederate victory at Thompson's Station on March 5. Later in the spring the regiment was ordered back to Mississippi, where it took part in the ultimately fruitless effort to defend Vicksburg and Jackson, Mississippi, against the Union advance.
After the fall of Vicksburg in July 1863 the East Texans bivouacked in Mississippi for ten months, during which time they were chiefly engaged in fending off Union raids into the interior of the state. On December 16, 1863, Col. Lawrence Sullivan Ross took over permanent command of a brigade formed from the Third, Sixth, Ninth, and Twenty-seventh Texas Cavalry regiments, and the men in these units thereafter fought together as Ross's Brigade until the end of the war. In May 1864 Ross's men hastened to north Georgia to serve as flankers in Gen. Joseph E. Johnston's defensive line against the advancing Union forces under the command of Maj. Gen. William T. Sherman. Under fire before Atlanta, the Third Texas engaged in almost continual skirmishes, as well as in the battles of Rome, New Hope Church, Lovejoy's Station, and Jonesboro, Georgia. After the fall of Atlanta on September 2, the regiment joined Gen. John B. Hood in his disastrous Tennessee campaign. Serving as part of the rear guard under Maj. Gen. Nathan B. Forrest, the Third Texas played a signal role in preventing the destruction of Hood's entire army during its precipitate retreat following the debacle at Nashville on December 15–16, 1864. Decimated and exhausted, the East Texas regiment remained bivouacked in Mississippi during the final months of the war. About half the men were granted furloughs; desertion took a further toll. When the Third Texas capitulated to Union major general Edward R. S. Canby at Citronelle, Alabama, in May 1865, there were but 207 members of the unit left to surrender.