Gainesville, the county seat of Cooke County is in the approximate geographic center on Interstate 35 located approximately 67 miles north of Dallas. In 1841, W.S. Peters and associates signed their first contract with the Republic of Texas "which provided that within three years, they would bring 600 families into North-Central Texas" into what came to be known as the Peters Colony. The first settlers arrived in the area after the newly created Peters colony offered 640 acres to each head of family and 320 acres to each single man, plus land for a church in each settlement. Before acquiring their tracts of land, these settlers were first required to swear allegiance to the Republic of Texas. They had to agree to construct a dwelling, to cultivate their fields, and to fence at least ten acres within three years.

With the constant threats of Indian attacks on this Red River frontier, the need for military protection became a most pressing problem. In 1847, Ft. Fitzhugh, named for Colonel William Fitzhugh, an experienced soldier and Indian fighter, was the first site of settlement in the region. The following year, the state legislature created Cooke County, named for William G. Cooke, a hero of the Texas War for Independence.

In 1850, Gainesville was established on a 40-acre tract of land donated by Mary E. Clark. City residents called their new community Liberty, which proved short-lived, as a Liberty, Texas already existed. Colonel Fitzhugh suggested that the town be named after General Edmund Pendleton Gaines. Gaines, a United States General under whom Fitzhugh had served, had been sympathetic with the Texas Revolution.

In the decade after the war, the county seat had its first period of extended growth, catalyzed by the expansion of the cattle industry in Texas. Gainesville, only seven miles from the Oklahoma border, became a supply point for cowboys driving herds north to Kansas. Two major cattle trails, the Chisolm Trail and the Shawnee Trail flanked Cooke County, and the cowboys would roar into Gainesville to visit the saloons, get supplies, gamble, and visit the "soiled doves." The merchants of Gainesville reaped considerable benefits from the passing cattle drives. An important gateway into the great grassland empire of Texas, Gainesville became an important hub of commerce and one of the most significant cattle towns in the state.