Under the leadership of Isaac Parker 224 settlers in the area signed a petition requesting the establishment of a new county, and in December 1855 the state legislature formed Parker County from Bosque and Navarro counties. Weatherford was designated as the county seat, and by 1858 the town had a new two-story brick courthouse surrounded by a handful of cabins and tents.

In September 1861, after the beginning of the Civil War, many young men from Parker County enlisted in Parsons' Brigade. Nine companies of eighty men each left the county to serve the Confederate cause during the war. Their absence contributed to population decline and disrupted the county economy and society.

In 1870 the agricultural census reported only 148 farms and ranches in the county, fewer than half the number ten years earlier, and only about 6,000 acres was classified as "improved." Corn and wheat production and livestock counts that year remained significantly below pre-war levels.  The last Indian raid in the county was recorded in 1874, and with the area stabilized the county's agricultural economy grew steadily during the 1870s, as thousands of people moved into the area. By 1880 there were 1,865 farms and ranches, encompassing almost 271,000 acres, in Parker County, and its population had grown to 15,870.