Until the late 19th century, the Comanche tribe of Native Americans occupied the area.

In 1907, with the coming of a branch of the Santa Fe Railroad, a number of farming operations were established.

Cotton Center was originally created in 1925 as a consolidated school district, with a small unincorporated community site, containing the school, cotton gins, and various businesses to support the surrounding farms.

[2] By the late 1940s, irrigation wells proliferated, pumping water from the Ogallala Aquifer.

The community revolves around farming and is tied together by the school, which as of 2005 had 140 students in prekindergarten through grade 12.