The area was first settled in 1847, making it one of the oldest communities in North Texas. A post office was established in 1881, and the settlement was named DeSoto in honor of Thomas Hernando DeSoto Stewart, a doctor dedicated to the community.
By 1885, DeSoto was home to approximately 120 people, a cotton gin, and a general store. Soon after, the population declined to below 50. In 1930, there were 97 people living in the community and several businesses.