Chireno is on State Highway 21 sixteen miles west of San Augustine and eighteen miles southeast of Nacogdoches in Nacogdoches County. Spanish pioneers first settled north of the site in 1790 on grants they received from the Spanish government. About 1837 John Newton Fall, of Georgia, was the first Anglo settler to secure land from José Antonio Chirino, for whom the town was named. Fall was reportedly responsible for much of the town's early development. In 1837 Samuel Martin Flournoy, of Mississippi, built a large two-story home that became Chireno's first post office. On May 22, 1846, the log and clapboard structure evolved into a stage stop known as the Halfway House. Other early Chireno families were those of Daniel Vail, brothers Randal and Sanford Wilson, G. W. Davis, William Stivers, and Joseph Stallings. By 1836 Chireno had several home schools with area ministers serving as teachers. The town organized the first public school by 1839. During the Civil War, amid rumors of an impending Union siege to capture Galveston, all the men in Chireno that were not too old left their homes to aid in defending the coast. Andrew Jackson Mast operated a tanyard with Joseph Stallings. They worked for the Confederate government six months out of each year providing boots for the troops. An associate, Craig Wilson, made saddles, harnesses, and other leather goods.
Reconstruction divided the community. The Freedmen's Bureau organized a branch in Nacogdoches, and by 1866 black soldiers had been sent to Chireno to ensure propriety in elections. In response, a chapter of the Ku Klux Klan was organized in Chireno to keep black voters from the polls. By 1870 Texas returned to the Union, and the period of unrest gradually came to a close.
In 1866 the appearance of oil near Chireno prompted the drilling of one of the first oil wells in Texas. Other wells were unprofitable and were eventually abandoned. Chireno's first cotton gin, a small hand-turned operation, preceded Jack Moss's successful water-driven mill and gin near the Cottingham Bridge in 1872. In 1912 the Angelina and Neches River Railroad came to Chireno from Lufkin, carrying both logs and passengers. The Frost Industries Incorporated Lumber Tram, later a part of the Santa Fe line, was constructed northwest of Chireno and was still used for hauling timber in the 1940s, when Chireno's principal crops were cotton, corn, wheat, barley, and potatoes. Livestock also remained important in the local economy. The population of Chireno was 415 in 1990 and 405 in 2000.