[9][10] The fort was strategically located as anchor to the cordon of army posts that had been established along the southwest Texas border after the Mexican War.

The fort's purpose was to guard the Mexican border, to protect the military road to El Paso, and to defend against Indian depredations arising from either side of the Rio Grande.

In the summer of 1854, Gen. Persifor F. Smith, the department commander, made a requisition to Governor Elisha M. Pease for six companies of Texas Rangers to conduct a campaign against the raiders.

Two companies of these Texas military volunteers, under captains Charles E. Travis and William Henry, were sent to Fort Clark, where they assisted the regulars in patrolling the road.

[9] In 1876, a visitor to the town described it as "the liveliest burg in West Texas, where the night life could only be compared to the saloons and gambling places that existed in the early days of the gold excitement of California and the Klondike.

On March 19, 1861, Captain Trevanion T. Teel, leader of 18 Confederate troops, accepted the surrender of the fort from then-Captain George Sykes, who was garrisoned there with four companies.

In June 1861, after the outbreak of the Civil War, Fort Clark was garrisoned by companies C and H, Second Regiment of Texas Mounted Rifles, with Capt.

I want something done to stop these conditions of banditry, killing... by these people across the river... you are to go ahead on your own plan of action, and your authority and backing shall be General Grant and myself...."[16]: 422–423  This led, on 18 May, to Mackenzie's raid into Mexico with six companies and 20 Seminole-Negro scouts (nearly 400 men) to avenge the Indian raid up the Nueces River Valley and the massacre at Howard's Wells, attacking the Kickapoo, Lipan, Pottawottami, and Mescalero Apache lodges at Rey Molina.

[16]: 424, 429, 433, and 441  The lodges were burned, at least 19 warriors were killed, 40-50 prisoners were taken, including the Lipan Chief Costalites[broken anchor], and nearly 200 horses were captured.

The Buffalo Soldiers, for a long time mostly unacclaimed, left a distinguished record of service in ridding southwest Texas of Indians.

Mackenzie's raid in 1873 had stopped Indian activity for almost three years, but as the lesson of Rey Molina dimmed, violence once more came to the Rio Grande border area.

When, in April and May 1876, Lipan warriors killed 12 Texans in an unusually bloody raid, Ord authorized Shafter to go after the offenders in their Mexican villages.

In the first of a long succession of border violations, Shafter's cavalrymen splashed across the Rio Grande and drove deep into the mountains of northern Coahuila.

Shafter's extensive campaign on the Texas borderlands frontier earned him the sobriquet "Pecos Bill", and he boldly implemented the Army's aggressive policy toward hostile Indians, which was one of removal or extermination.

[15]: 125 In 1941, the 112th Cavalry Regiment (Horse) Texas National Guard under the command of Col. Julian Cunningham, was assigned to Fort Clark, where it trained until it was deployed for combat in the Pacific.

Finally, in June 1944, nearly three years after the beginning of World War II, and after full mechanization of the cavalry, the government ordered the closure of Fort Clark, one of the last horse-cavalry posts in the country.