This paper examined the historical evolution, natural and climatic characteristics of cotton production in Gansu Province. According to the “production zoning with similarity”principle, the active accumulated temperature above 10℃, mean temperature in July, and frost-free period, and under the national framework of first-tier cotton production zone, the cotton production zone in Gansu Province should be divided to the second-tier zones, including Hexi Corridor sub-region of northwest inland region, Loess Plateau sub-region of Yellow River region, and extra early-maturing sub-region. Furthermore, it was divided into 4 third-tier regions including early-maturing cotton region of Hexi Corridor, extra early-maturing cotton region of Hexi Corridor, extra early-maturing cotton region of middle Yellow River irrigation region, and Londong extra early-maturing cotton region. This paper also pointed out the advantages, disadvantages, and possible natural disasters of cotton production in Gansu Province. Finally, this paper provided some suggestions for the future development of cotton production in Gansu Province, including 1) to adopt reasonable zoning plan; 2) to optimize planting area and structure; 3) to increase production scale to achieve scale economy; 4) to encourage technology progress and innovation; 5) to integrate production, learning, and research, 6) to combine breading, reproduction, and extension; 6) to attract more experts and professionals and provide more trainings; and 7) to increase investment to support cotton production.