Clarksville, the county seat of Red River County, is at the junction of U.S. Highway 82, State Highway 37, and Farm roads 114, 412, 909, 910, and 1159, fifty-eight miles northwest of Texarkana near the center of the county. It was established by James Clark, who in 1833 moved to the area and laid out a townsite. Isaac Smathers is supposed to have built one of the first houses, a building that later became the home of Charles DeMorse. With the organization of Red River County in 1835, Clarksville defeated La Grange (later Madras) as the county seat. The town was incorporated by an act of the Texas Congress in 1837, and within a few years it became an educational and agricultural center. Clarksville Female Academy was founded in 1840 on Pine Creek and in 1844 moved to Clarksville; McKenzie College, four miles from Clarksville, opened in 1841; and the following year DeMorse began publication of the Clarksville Northern Standard. A post office opened in 1846, and in 1848 semiweekly mail service was instituted between Clarksville and Natchitoches, Louisiana.
In the town's early days, itinerant preachers, among them Mansell W. Matthews, John B. Denton, Gilbert Clark, and Craig Shook, conducted religious services in a log schoolhouse. The First Presbyterian Church, believed to be among the oldest continually operating Protestant churches in the state, was organized at nearby Shiloh, four miles to the northeast, in 1833, and moved to the town in 1848. Baptist and Methodist churches were also organized before the Civil War.
From the late 1830s until the Civil War, Clarksville was the most important trading center in Northwest Texas. Steamboats brought goods from New Orleans by way of the Red River and delivered them to Rowland's Landing fifteen miles to the north. They were then hauled overland by wagon. During the 1850s new steam sawmills and cotton gins added to the town's importance. The first courthouse, a modest frame structure, was erected around 1840. In 1850 it was replaced by a larger brick structure at the center of a large public square; a brick jailhouse was built nearby in 1852. Within a few years of the town's founding, numerous mercantile establishments opened on and around the courthouse square, and by eve of the Civil War Clarksville's population had grown to 900.
The economy suffered a serious setback during the war and the early Reconstruction years, but by the beginning of 1870s business in Clarksville had begun to recover. The greatest impetus to the town's development came in 1872 with the completion of the Transcontinental Branch of the Texas and Pacific Railway. The coming of the railroad brought many new settlers and merchants to the area, and by 1885 Clarksville had a population of 1,200, five white and two black churches, a Catholic convent, three schools, two banks, two flour mills, and a weekly newspaper, the Clarksville Times; principal products included cotton, livestock, and grain. A new three-story limestone courthouse, designed in the Renaissance Revival style by W. H. Wison, was completed in 1884, a symbol of the town's continuing prosperity. In 1914 Clarksville had 3,000 inhabitants, a waterworks, two newspapers, an ice plant, and an electric power plant. But with the rise of Dallas, Paris, Bonham, and Texarkana during the 1870s and 1880s, the importance of Clarksville as a trading center had begun to decline.
In 1929 the estimated population reached 4,000. With the onset of the Great Depression in the early 1930s, many Clarkvillians found themselves out of work, and a large number left the area. By 1931 the population had dropped to 2,950. The number of rated businesses also declined from a high of 165 in 1931 to 104 in 1936. Particularly hard hit was the cotton wholesale and processing industry, which suffered from the combined effects of falling prices and the boll weevil.
In 1936 the economy began to turn around. Production of cotton increased 100 percent over the previous year, with the estimated value of the crop put at $1.9 million. During the mid-1930s oil was also discovered at Talco, sixteen miles south, and in 1936 more than 1,000 leases were filed with the county clerk's office. The oil boom brought a new wave of prosperity to the town, helping to mitigate the worst effects of the depression and fueling a wave of public and private construction. The population rebounded during the late 1940s, to an estimated 4,300 in 1952; the number of rated businesses that year also hit an all-time high of 210.
After World War II, however, Clarksville began to feel the effects of urban flight and the steady decline of agriculture. Between 1920 and 1980 the population of the county declined by one-half, and the number of farms dropped off sharply. The town subsequently weathered the decline of the oil industry. Heavily dependent on agriculture and oil for its livelihood, Clarksville saw a dramatic fall in its business and tax proceeds. During the 1980s one of the town's banks folded under the weight of bad farm and energy loans. The town was also rocked by scandal after a former Clarksville police chief was jailed for shooting a prisoner in the back, and a piece, aired nationally by CBS News, reported that the local housing authority was segregating white and black residents. In 1990 Clarksville had a population of 4,311, and ninety-five businesses. Leading industries in 1991 included livestock raising, light manufacturing, and oil and gas production. In 2000 the population was 3,883.