Artifacts discovered in various parts of the county indicate that people hunted and gathered in the future Uvalde County as long ago as 7000 B.C. The Edwards Plateau and the surrounding hills were the favorite hunting grounds of the Comanche, Tonkawa, and Lipan Apache Indians. Either Álvar Núñez Cabeza de Vaca in 1535 or Andrés do Campo in the middle 1540s may have been the first European to set foot in Uvalde County. Evidence of a permanent Indian village on the Leona River at a place south of the Fort Inge site is indicated in the written accounts of Fernando del Bosque's exploration in 1675. After the establishment of San Antonio in 1718, the Uvalde County region was consistently traversed by Spanish soldiers, commercial packtrains, buffalo hunters, cattlemen, and mineral prospectors. In 1762 Nuestra Señora de la Candelaria Mission was established near the site of present Montell and near the site of a prehistoric Indian village at Candelaria Springs. The mission was abandoned in 1767 due to Comanche attacks. On January 9, 1790, Juan de Ugalde, governor of Coahuila and commandant of the Provincias Internas,^qv led 600 men to a decisive victory over the Apaches near the site of modern Utopia at a place known then as Arroyo de la Soledad. In honor of his victory, the canyon area was thereafter called Cañon de Ugalde.

Although the huge tract of land granted Irishmen John McMullen and James McGloin^qqv in the 1820s by the Mexican government included a portion of the area of present Uvalde County, the county remained unsettled until the late 1840s. French botanist Jean Louis Berlandier visited the area in the late 1820s, and frontiersman James Bowie guided a group of silver prospectors into the area of north central Uvalde County in the 1830s. A trail used by Gen. Adrián Woll's Mexican army on its way to attack San Antonio in 1842 crossed the territory of Uvalde County and became the main highway between San Antonio and the Rio Grande. Fort Inge, established in 1849, was one of many frontier forts commissioned to repress Indian depredations on the international border with Mexico. Located at the base of Mount Inge and served by the Overland Southern Mail, Fort Inge proved to be a focus for the early settlement of Uvalde County. One of the first settlers to the environs was William Washington Arnett, who arrived in the winter of 1852. The Canyon de Ugalde Land Company, formed by land speculators in San Antonio in 1837, began purchasing headright grants in Uvalde County in the late 1830s. Many of these land grants were in prime locations along the river valleys of Uvalde County, and the company held the rights until the 1850s before reselling them to frontier settlers; profits often averaged 200 percent. Among the many purchasers of these brokered land grants was a twenty-two-year-old merchant from New Jersey, Reading W. Black, who with a partner, Nathan L. Stratton, purchased an undivided league and labor on the Leona River in 1853. Black understood that his land was strategically situated near the last permanent source of water and military protection for an ever-increasing number of westward-bound settlers, soldiers, and commercial traffickers. Due in large part to his successful efforts to redirect roads to Eagle Pass, El Paso, and California through his property, Black's burgeoning commercial enterprises and general store quickly became a marketing center for the soldiers at Fort Inge and area ranchers and farmers, as well as traders from San Antonio and Medina County to the west and numerous Indian and Mexican traders from the north and east. Early pioneers and settlers of the county sought out the spring-fed rivers and flowing springs, made lumber from the substantial supply of hardwoods that grew along their banks, and survived on wild cattle and game. Cattleman and frontiersman John Bowles recalled the huge herds of cattle that roamed the open prairie of south Uvalde County in 1855.

Uvalde County was formed by legislative act from Bexar County on February 8, 1850, but failed to secure a permanent county status because of an insufficient number of settlers. Of equal importance to the early history of the county was the development of the farming and ranching settlements at Waresville by Capt. William Ware in the upper Sabinal Canyon and Patterson Settlement by George W. Patterson, John Leakey, and A. B. Dillard on the Sabinal River; these settlements coincided with Reading Black's development of the Leona River at Encina. A second attempt by Black to organize the territory resulted in a petition to form a county encompassing the area of the present Kinney, Maverick, and Uvalde counties. The petition was approved in 1855 by the citizens of Eagle Pass, Los Moras, Patterson Settlement, and Encina. A much smaller Uvalde County was established by legislative enactment on February 2, 1856; four months later, on June 14, Encina was made county seat and renamed Uvalde. Slow but steady progress marked the pre-Civil War years. The second floor of the courthouse was made into a school, and six school districts were organized for the county in 1858. The San Antonio-El Paso Mail route was extended along the county's main road with a stop at Fort Inge in 1857. The estimated population increased from seventy-five in 1853 to 442 by 1858. Thomas B. Hammer established a store at the intersection of the Sabinal River and the San Antonio-Eagle Pass road. Comanche and Apache raids significantly hindered development. Seminoles, Tonkawas, and Lipan Apaches swept down the Leona River valley and attacked ranches near Fort Inge soon after its temporary abandonment in 1857. Many settlers along the Nueces River moved to Laredo, and many along the Leona moved to San Antonio or concentrated in a defensive stockade, known as Fort Anglin, built on Anglin's Creek.

Conflict between Mexicans and Anglos during and after the Mexican War continued in Uvalde County, with the reported lynching of eleven Mexicans near the Nueces River in 1855. Laws passed in 1857 prohibited Mexicans from traveling through the county and were probably a part of an effort to remove them from the lucrative freight business along the San Antonio-Eagle Pass road. By 1860 Uvalde County had a population of 506; at this time most county residents were engaged in the raising of livestock. Since it was generally believed that farming was impractical without irrigation, the plantation system never developed in Uvalde County; as a result, only twenty-seven slaves resided within the county at the time of the Secession Convention in 1861. Uvaldeans voted 22 to 18 for American party candidate Millard Fillmore over Democratic candidate Buchanan in 1856, and 76 to 16 against secession. These votes probably reflected the concern that secession meant losing the security and commercial impetus provided by the federal troops at Fort Inge and other frontier forts in the region. Beginning with the Civil War and Reconstruction Uvalde County endured three decades of unrelenting lawlessness and frontier savagery. The abandonment of Fort Inge immediately after secession was followed by renewed Indian attacks. Confederate forces that occupied the fort in 1861 and militia men stationed at temporary Confederate outposts at Camp Dix on the Frio River and at Camp Sabinal on the west bank of the Sabinal River helped provide protection for the growing number of Confederate wagontrains en route to Mexico via the San Antonio-Eagle Pass road after Union takeover of Mexican entry points along the lower Rio Grande. Many men in Uvalde County fought for the Confederacy, while such Unionists as Reading Black fled to Mexico to avoid persecution. Between 1862 and 1863 the county suffered a threefold increase in the number of delinquent taxpayers. It lost half of its school-fund when the state treasury was redirected to the Confederate war effort. Violence and lawlessness were so pervasive that armed guards were employed to assist the county tax assessor and collector, and the county had no sheriff for nearly two years. The years immediately following the Civil War were marked by conflicts between Confederates and Unionists returning to live in Uvalde County. Black's attempt to form a strong local Union League may have led to his assassination in October 1867. At the end of the Civil War, Uvalde County remained the last frontier district court site for a region that included the unorganized territories of Zavala, Kinney, Edwards and Maverick counties. The region was home to smugglers, cattle and horse rustlers, and numerous other desperadoes. One of the county's most colorful and powerful characters during this period of lawlessness was its most notorious cattle rustler, J. King Fisher.

Uvalde County gradually emerged. The Uvalde Umpire began publication in 1878 and the Hesparian in 1879. King Fisher was appointed county deputy sheriff in 1881 and was succeeded by Sheriff Henry Baylor in 1884. The Galveston, Harrisburg and San Antonio Railway was built through the county, passing through Sabinal and Uvalde City, in 1881. Ranchlands were fenced, and the use of school lands for free grazing was banned in 1877, when a new courthouse was built; Uvalde was incorporated in 1884. Fence cutting prompted County Judge John Nance Garner to issue an appeal for assistance to Attorney General Woodford H. Mabry in Austin in 1883, but the incidents declined, and the open range receded as a new ranch industry began to emerge. The seeds of the ranching industry were in great part sown by the maverick cattle left by the Spaniards. Uvaldean cowboys such as Chris Kelly and Gideon Thompson of Utopia crossbred these cattle with imported English Devon and Durham bulls to produce cattle well suited for the long cattle drives from the region. In the 1880s William M. Landrum of Laguna introduced Angora goats to the area. By the turn of the century Uvalde County had 58,925 cattle and 81,705 goats. By 1905 the Southern Pacific had established railheads in Uvalde, Knippa, and Sabinal, as well as near many of the larger ranches; ranchers throughout the county were now within a day's drive of the railroad depots. Brush-arbor camp meetings, held periodically throughout Uvalde County and annually at Sabinal, Utopia, and Montell, were often attended by hundreds of people. The local bee industry developed a product that received first place in the 1900 Paris World's Fair. The first shipment was a case of bulk comb honey from D. M. Edwards in Uvalde in July of 1883. Entrepreneur James Whitecotton of Laguna gained attention as the largest honey dealer in the country with record sales estimated at a million pounds annually during the 1890s. The abundant guajilla shrub furnished the nectar for Uvalde County honey, which in 1900 produced 161,800 pounds.

During the first decade of the twentieth century the county's population grew from 4,617 in 1900 to an estimated 11,233 in 1910. One-fourth of all mohair produced in the United States in 1903 originated in Uvalde County. Between 1900 and 1903 irrigated farm acres increased from 365 to 2,500. By 1903 farms were successfully growing peaches, plums, figs, pears, onions, tomatoes, pumpkins, melons, potatoes, cabbage, and beans. Onions shipped from Uvalde County reached a high of 100,000 pounds in 1903. Limestone asphalt mined at Blewett in southwest Uvalde County was shipped to road-paving contractors throughout Texas from 1898 to 1901. In 1910 county farmers harvested 23,135 pounds of pecans. After the outbreak of the Mexican Revolution in 1910, a large number of Mexicans moved to Uvalde County and were instrumental in clearing large tracts of land and digging ditches, as irrigation spread throughout the county. The construction of the Uvalde and Northern Railway to Camp Wood and of the Asphalt Beltway Railway in 1921, and the expansion of the asphalt mines in far southwestern Uvalde County at Blewett and Dabney (see UVALDE COUNTY LIMESTONE ROCK ASPHALT), also employed Mexican Americans. By 1930, 40 percent of Uvalde County's 12,445 residents were Mexican American. As a consequence of deed restrictions forbidding Anglo homeowners from selling to blacks, Asians, and Hispanics, Mexican Americans were limited in their purchase of town lots to those located in colonias. The dismal labor market in the county during the Great Depression caused many Mexicans living in Uvalde County and Texas to return to the relatively calm political environment and improving economic conditions in Mexico. Many others were repatriated to Mexico (see MEXICAN AMERICANS AND REPATRIATION). Ranchers in the period buckled under the depressed prices and high feed costs. The economic crisis forced many beekeepers to quit the business. Only large-scale ranches survived the depression, and the number of farms and ranches declined from 977 in 1925 to 761 in 1930. Farm production of corn, cotton, honey, pecans, oats, and milo dropped in the same period, but the wool and mohair industry surged. Although overall production was declining, many ranchers and farmers sold pecans to survive. Two notable government projects were completed in the county in the later part of the 1930s: the National Fish Hatchery, three miles west of Uvalde (1937), and Garner State Park, which was built with Civilian Conservation Corps labor and opened in 1941. Garner Army Air Field opened in 1941.

Ranchmen in Uvalde County were primarily breeding Hereford cattle by 1940; several breeders sold their stock throughout the United States. In the early 1940s the proximity of auction houses such as Roy Kothmann's in Uvalde City succeeded in replacing the terminals in San Antonio and Fort Worth as the market terminus for Uvalde County ranchers. To cut costs, ranchers switched to trucks to carry cattle. In 1948 the dominant agribusinesses in Uvalde County were livestock and the wool and mohair industry; that year an estimated 48,448 acres of farmland was under cultivation. Productive farms in the eastern part of the county cultivated cotton and grain, and those in the southern part of the county grew vegetables irrigated by shallow wells and the Frio and Nueces rivers. A 2,500-acre pecan plantation, irrigated by one of the largest artesian wells in South Texas, had 30,000 trees in Uvalde County in 1940. During the 1950s a devastating drought claimed large numbers of cattle and live oak trees, as water wells went dry; the production of corn, wheat, cotton, and oats declined dramatically, and the number of farms dropped from 690 in 1950 to 525 in 1959. The raising of pecans remained a major industry in the county in the 1990s.

By 1960 Mexican Americans made up one half of Uvalde County's 16,015 population. Efforts to gain civil rights for Hispanics in Uvalde County began with the establishment of the Tomas Valle Post of the American Legion. As late as November 23, 1973, a federal administrative judge ruled that Uvalde County schools were still segregated. County churches maintained segregated places of worship until an integrated Catholic church emerged in Uvalde in 1965. The continued use of mechanization in the county's agricultural industry during the 1960s encouraged many seasonal and migrant workers to move to Uvalde City and Sabinal. A militant chapter of the Mexican American Youth Organization formed in Uvalde City in 1968 eventually led to a walkout by more than 500 Mexican-American students on April 14, 1970; the protest lasted six weeks. The Texas Rangers responded to requests by the school board to help control the volatile situation. Senator Walter F. Mondale, chairman of the United States Senate Committee on Equal Educational Opportunity, went to Uvalde on July 30, 1970, and criticized city officials in an interview published in the Uvalde Leader News. By 1975 only six Mexican Americans had served in public office in the county and none in leading roles. Since then several Mexican Americans have served as county commissioners and in other county and local offices (see MEXICAN AMERICANS AND POLITICS).

In 1973 Uvalde County had one of the largest wool and mohair merchandising warehouses in Texas. By 1975 the county rated third among counties in Texas in Angora goat and mohair production. The National Fish Hatchery, produced a million fish annually in the early 1970s-fish produced were channel catfish, largemouth bass, and sunfish. Ranchers began leasing their land to hunters. By the 1970s the Hereford breed had decreased in popularity, and ranchers had begun to crossbreed with Brahman cattle, a breed able to graze farther from water in hot weather. Since 1973 Uvalde County livestock raisers have introduced a number of European breeds to produce cattle more adaptable to feedlots, which have become more common. The population grew from 17,348 in 1970 to 22,441 in 1980. A substantial increase in improved acreage, from 54,187 acres in 1970 to 123,576 acres in 1980, resulted in increased production of corn, wheat, and cotton. Vegetable processors operated throughout the county. Several grain-elevator operators and seed-company representatives were in the county in 1974. Approximately $45 million was generated by farming in Uvalde County in 1974.

County voters supported Democratic presidential candidates in all elections except in the years 1928 and 1952. After 1952, however, voters consistently supported Republican candidates, with one exception in 1964. The Texas Agricultural Extension Service recorded an estimated market value of $11,062,000 for cotton, $6,183,000 for corn, and $1,100,000 for wheat in 1989 for Uvalde County. A variety of vegetables with estimated cash receipts of $7,982,000 were grown in the county that year-spinach, onions, cantaloupes, carrots, cabbage, and cucumbers. Ranchers in 1989 received an estimated $2,222,700 in hunting leases on 740,000 acres of land. These profits helped them survive losses in other areas of their operation. County ranchers fed an estimated 43,500 beef cattle, 17,000 pigs, 85,000 goats, and 38,000 sheep in 1989. The allocation of the county's underground water was the dominant concern for farmers, ranchers, merchants, and politicians throughout the 1980s. Below-average rainfall in the late 1980s accelerated efforts to maintain local control of underground water supplies. In January 1989 Uvalde County joined Medina County by withdrawing from the Edwards Underground Water District. A rare winter freeze in 1989, when temperatures dipped to 6° F, so extensively damaged the county's winter vegetable crop that Uvalde county judge Bill Mitchell declared the county a disaster area. In 1990 Uvalde County had a population of 23,340, with 60 percent identified as Hispanic.