Seminole, the county seat of Gaines County, is at the intersection of U.S. highways 62, 180, and 385, State Highway 214, and Farm Road 181 in central Gaines County. In 1905, prior to the organization of Gaines County, W. B. Austin opened a post office in his store, which was about a mile south of the site of Seminole. The post office was named Caput.
Later that year a syndicate of New York investors donated land for the county seat of the newly organized county. The new community was platted and lots went on sale in 1906. Early merchants included Austin, who relocated to the new site, Guy Stark, and W. H. Brennard. In 1906 Seminole post office opened and a wooden courthouse was built. The Seminole Presbyterian Church, built in 1906–07, served as a meeting place for a number of local denominations and hosted a Union Sunday school. A Methodist church was built in 1908, and a Baptist church followed in 1922. Seminole schools began with a small two-story building erected in 1906 to serve the eastern part of the town, and a second school was built on the west side in 1910. A weekly newspaper, the Seminole Sentinel, started publishing in 1907 and was still in operation in the 1990s. The Seminole National Bank opened in 1906 and was followed by the First State Bank in 1907. Bank robbers got away with more than $3,000 from the Seminole National Bank in 1912. The two banks consolidated as the First State Bank in 1914.
By 1914 Seminole had about 300 inhabitants, telephone service, and a movie theater. The town briefly enjoyed rail connections to Midland when the Midland and Northwestern Railway built through in 1918. The line proved unprofitable and was abandoned in 1923, the same year a serious fire destroyed a number of downtown businesses. By 1930 the town had an estimated 400 people and twenty businesses. A new school building was completed in 1931. The First State Bank closed in 1933, a victim of the Great Depression, but the development of Seminole oilfield and the Gaines County oil industry spared the town many of the worst effects of the depression. Seminole incorporated in 1936 with a commission form of city government. C.C. Clothes was the first mayor, and the first bond issue installed a water system for the city. In 1937, due to consolidations of rural schools, Seminole school district was believed to be the largest in the country, covering some 753 square miles, though it served only 370 students. The town's population increased dramatically to 1,761 in 1940 and doubled to 3,480 by 1950, as the city surpassed Seagraves as the most populous community in Gaines County for the first time. Twin industrial plants, Phillips Gasoline and Columbia Carbon Company, located outside the city, were important employers of Seminole residents in the 1950s. The city government changed to an alderman type in 1952, a new hospital was built in 1953, and in 1954 the city water system was enlarged. The Gaines County library was opened in Seminole in 1958, the same year the county courthouse was extensively renovated. The city continued to grow in the 1950s, reaching a population of 5,737 by 1960, then temporarily declined to a population of 5,007 in 1970. The 1980s and 1990s were characterized by slow growth, as the population reached 6,080 in 1980 and 6,342 in 1990. In the 1990s Seminole continued to serve as a market center for an agricultural and oil and gas producing region. The top employers were Seminole Independent School District, Amerada Hess, an oil and gas producer, and Gaines County. Radio stations KSEM and KIKZ broadcast from the town.