Gossypium thurberi, a threatened wild cotton species native to northern Mexico and southwestern USA, is globally important because its agronomic traits can be introgressed into cultivated species to improve fiber quality and resistance to biotic and abiotic stressors. However, studies on the current and future potential distribution of the species are scarce. The objectives of this study were (1) to develop a distribution model of G thurberi using a Geographic Information System platform, (2) determine environmental factors that influence the current distribution of the species in Mexico, and (3) estimate the potential distribution of the species under current and future climates. We analyzed the following variables: Annual Available Soil Water (mm year−1, AASW), Flowering Growing Degree Days (FGDD), absolute minimum temperature (°C, Tminabs), and altitude (amsl, ALT). Results showed that the current potential distribution of G. thurberi in northern Mexico, estimated at 112,727 square kilometers, is projected to be drastically reduced by 77 and 86%, considering a possible increase in temperature of 1.5 °C and 2 °C in near-future (2021–2040) and mid-future (2041–2060) climates, respectively, and a 100 mm reduction in average annual precipitation under both climates. The greatest reduction will be in areas in Sonora (Mexico) adjoining Arizona (USA), where the largest populations of the species are currently reported. AASW, FGDD, and ALT jointly influence the distribution of G. thurberi, with AASW as the dominant factor under future climate change. The areas that may continue to harbor populations of G. thurberi under future climate will present AASW of 0.2–55.6 mm year−1, FGDD of 242–547, and ALT between 550 and 1561 amsl. The projected future potential distribution in the country includes new suitable areas, including one in the Trans-Mexican Volcanic Belt, that may serve as refuge areas. The findings can contribute to the design of more precise collection efforts and conservation strategies to prevent species extinction.