The area of central Texas which was to become Mills County was first home to the Tonkawa Indian Tribe. The Comanche and Apache Tribes pushed the Tonkawa off their land. By the mid 1800s, most of the Indians were relocated to Oklahoma.
White settlers came to the area in the 1850s. One of the first settlements was Williams Ranch, about 4 miles south of the current town of Mullin. In 1885, the Santa Fe Railroad bypassed Williams Ranch and another booming town, Center City, and created two new towns, Goldthwaite and Mullin.
In 1887, Mills County was formed from Brown, Comanche, Hamilton, and Lampasas Counties. The county was named in honor of John T. Mills, an early judge.
Goldthwaite became the county seat in 1889. It was named for Joe G. Goldthwaite, the railroad official who conducted the auction of town lots. A county courthouse was completed in 1890; the courthouse burned in 1912 and was replaced with a brick structure the following year. The first county jail, constructed in 1888, received a Recorded Texas Historic Landmark designation in 1965, and has been on the National Register of Historic Places since 1979.