The settlement was established in 1878, when New York investor and financier William Whitewright Jr. (1815–1898), after whom the community was named, purchased a tract of land in the path of the Missouri–Kansas–Texas Railroad, which was then extending its tracks across the county from Sherman to Greenville.

Likely due to the combination of its rail connection and its location in the center of perhaps the richest farmland in the county near the headwaters of Bois d' Arc Creek, Whitewright soon attracted settlers and businesses.

By the mid-1920s, both the Missouri-Kansas-Texas and the Cotton Belt served the town, and 68 businesses, including two banks and manufacturers of cottonseed oil and flour, operated locally.

Whitewright served as a marketing, retail, and commercial center for the farmers of the surrounding area, who produced such crops as cotton, wheat, and corn.

On June 12, 1911, a fire that started in a trash pile and was fanned by high winds destroyed most of the Whitewright business district.

[7] Whitewright was the home of US Lieutenant Joe Tom Meador, who after World War II looted several major pieces of art from a cave near Quedlinburg, Saxony-Anhalt, Germany.

Meador, a soldier with good knowledge of art, recognized the importance of the treasures (among them being the Gospel of Samuel and the Crystals of Constantinople).