[Objective] The desertification status and its driving factors in Gansu Province were analyzed in order to provide a scientific basis for the comprehensive prevention and control of desertification and the promotion of ecological projects such as the “Three Norths” shelterbelt program. [Methods] Trend analysis and spatial autocorrelation analysis were used to characterize the spatial and temporal distribution of desertification in Gansu Province from 2000 to 2022, and geographically and temporally weighted regression was used to analyze the influencing factors. [Results] ① The overall desertification in Gansu Province was characterized as “desertification in the northwest and green in the southeast”. The northwest region was affected by both wind erosion and salinization, and exhibited the most serious desertification, which gradually decreased towards the southeast. The central region was affected by soil and water loss, and had a serious degree of desertification, while the south region had a less serious degree of desertification. The degree of desertification in Gansu Province gradually decreased during the 23-year study period, and the amount of decrease was greater in the southern region than in the northern region. ② In terms of spatial autocorrelation, desertification in Gansu Province was mainly characterized by aggregation, i. e., the degree of desertification showed obvious positive spatial correlation. ③ Increased precipitation was most beneficial in mitigating desertification and had a greater impact in the northwest than in the southeast, while wind speed and population exacerbated desertification. Desertification was exacerbated by warmer temperatures in the southwest and vice versa in the rest of the region. [Conclusion] From 2000 to 2022, desertification in Gansu Province showed an improving trend, while desertification in the northwestern part of the province was still serious. There was obvious spatial and temporal heterogeneity in the drivers of desertification in Gansu Province, and the most important factor affecting desertification was precipitation.