A railroad depot by the name of Spofford Junction was established at the site by the Galveston, Harrisburg and San Antonio Railway in 1882. The GH&SA built westward from San Antonio, split at Spofford, and reached Eagle Pass on a branch line in 1882 and Langtry on the main line in 1883. Entrepreneur George Hobbs moved to the site during the period of railroad construction and sold supplies to employees of the railroad from a tent store. The community was named after C. K. Spofford, who opened the Spofford Hotel and a store near the railroad depot in the early 1880s. The community developed around the hotel and served as a shipping point for area ranchers, who raised goats, sheep, and cattle. A Spofford post office was opened in 1884. By 1890 Spofford had an estimated population of 100, two saloons, and the firm of Hobbs and Company. In 1896 the town had an estimated population of 125, numerous saloons, two hotels, and a general store. By 1896 a school had been established; that year the enrollment was twenty. In 1900 the one-teacher Spofford school had fourteen students. There is evidence that Spofford was one of several communities visited by President William McKinley in January 1901.
Spofford began to expand south of the railroad by 1906, when a large portion of land was subdivided and prepared for settlement. In 1907 the community added a blacksmith shop, a barbershop, and a livery stable to its expanding business district. Methodist and Baptist churches probably existed in the community at that time. In 1912 the first motion picture theater was opened by Messrs. Reming and McIntosh. By 1914 several of the estimated population of 200 had telephones. By 1925 the community's estimated population had dropped to 100, but by the late 1930s it had rebounded to 319. At that time the population was roughly 75 percent Hispanic and 25 percent Caucasian. Spofford continued to be the principal shipping point for cattle in Kinney County. By the mid-1940s Spofford had 373 residents, shipping pens, express and railway offices at the Southern Pacific depot, a Red and White general store, a grade school with three teachers (the high school students were bused to Brackettville), and Baptist, Methodist, and Catholic churches. The community was incorporated in 1945 to provide for a sanitary water supply. In 1961 the population was down to an estimated 138, and only two businesses were in operation. By 1974 the town had shrunk to fifty-two people. Maps of that year showed a church, a cemetery, a radio tower, and a scattering of dwellings. In 1989 Spofford had an estimated population of seventy, and in 1990 the population was sixty-eight. The population was seventy-five in 2000. Source: Handbook of Texas Online.