Two officers had already been shot down carrying the regimental flag of the 22nd Alabama Infantry, when Lieutenant A.B. Renfro seized the fallen colors, raced forward and "planted them almost within the enemy's line." His courageous act came on September 20,1863, amid the fiercest fighting of the Battle of Chickamauga, where 34,624 casualties were recorded. Lieutenant Renfro and his commanding officer, Lieutenant Colonel John Weedon, led the battle-hardened troops of the 22nd Alabama within 20 paces of the Federal position, where both sides poured fire into each other at close range.
Captain Harry T. Toulmin witnessed the carnage which left him in command of the regiment. "Here," he reported, "Lieutenant A.B. Renfro.-.fell pierced through the head with colors in hand. Here too, fell our brave, our true, our esteemed commander, Lieutenant Colonel John Weedon.... He fell beneath the honored folds of that cherished flag under which he had so gallantly led his brave men."

The regiment stubbornly held its ground, then slowly began to drive back the opposing Federals. Confederate reinforcements suddenly arrived and the 22nd Alabama pressed forward with renewed strength. "At this time," Toulmin reported, "the Twenty-second Alabama rushed forward with a yell and drove the enemy in dismay from his strong position.... The regiment continued to press forward, the enemy fleeing before it, until ordered to fall back...."
The 22nd was re-formed, then ordered to assault a strongly fortified Federal position on a high ridge defended by a battery of artillery. "The fire of grape and canister at this point was terrific," Captain Toulmin recalled, "and although the command made bold and earnest efforts to [take] the hill and storm the battery it was unsuccessful. Here, I regret to state, we lost our colors." The Battle of Chickamauga ended in a Confederate victory, but of the regiment's 31 officers and 340 men, a staggering number —15 officers and 190 men — were killed, wounded or missing.

The 22nd Alabama Infantry was organized in Montgomery, Alabama, on October 6,1861. The troops had been recruited by Zachariah C. Deas, a successful Mobile cotton broker who had served in the U.S. Army during the Mexican War. At his own expense, he fully equipped the 22nd Alabama and was commissioned as its first colonel and commander. The regiment initially served in the Army of Mobile, then in March of 1862, was assigned to the Army of the Mississippi.
The regiment experienced its first combat — "seeing the elephant" as the soldiers called it — at the Battle of Shiloh. Colonel Deas led part of the 22nd Alabama Infantry and portions of other regiments into ferocious fighting at Shiloh, where two of his mounts were killed and he was seriously wounded. "With these fragments of regiments, numbering together less than 500,1 attacked two brigades," he reported afterward. "But after continuing this unequal contest for nearly half an hour, and nearly one-half of my command had been killed or wounded, I gave the order to fall back, which was done in good order. I now formed and moved forward again, with the remnant of my brigade (now reduced to about 60 men).... Here my second horse was killed, and I (having been wounded some time previously) was unable to march." Deas recovered, was promoted to brigadier general, and for much of the war commanded a brigade that included the 22nd Alabama.

After Shiloh, the 22nd Alabama Infantry participated in the Corinth Campaign, and was engaged at Munfordville in September of 1862, and at the bloody Battle of Murfreesboro in December. In June of 1863, the regiment served in the Tullahoma Campaign, and was severely mauled in a series of courageous assaults at the Battle of Chickamauga on September 20,1863. Captain Harry T. Toulmin found himself in command of the regiment at the battle's end, after his superior officers were shot down.
 
Along with the Confederate Army of Tennessee, the 22nd participated in the Battle of Chattanooga, was engaged in the Atlanta Campaign, and saw action at New Hope Church, Peach Tree Creek, and Ezra Church. The regiment served under General John Bell Hood at the disastrous battles of Franklin and Nashville in late 1864, and its survivors were engaged in North Carolina in March of 1865 at the Battle of Kinston and the Battle of Bentonville. At the war's end, the remnants of the regiment were combined with portions of three other regiments into the 22nd Alabama Infantry Regiment Consolidated. The reorganized regiment was surrendered by Confederate General Joseph E. Johnston at Durham Station, North Carolina, on April 26,1865. The soldiers of the 22nd Alabama endured some of the war's bloodiest combat, served the Confederacy until its end, and — in the words of a veteran — "served [their] country 'til the close of the war with fervency and zeal."