The main stream of the Tarim River is a crucial part of China's ecological security strategy within the "two screens and three belts" framework, serving the "northern sand control belt" and the ecological civilization corridor. Evaluating and understanding desertification dynamics and driving factors is essential for achieving the United Nations Sustainable Development Goals and promoting ecological civilization. This study, based on the United Nations Convention to Combat Desertification, quantified the desertification process of the Tarim River's main stream from 1990 to 2020 using Landsat series satellite imagery from Google Earth Engine. Additionally, we employed panel data models to analyze the driving roles of climate change, socio-economic factors, and policies in desertification.Results indicate that between 1990 and 2020, desertification in the main stream of the Tarim River initially intensified, with 15% of the area experiencing desertification between 1990 and 2000. However, this trend was subsequently reversed, with only 0.6% of the area undergoing desertification over the 30-year period. Extensive economic development (-37.2%) and population growth (-48.7%) were the predominant factors exacerbating desertification in the initial period (1990-2000), whereas positive policies (55.3%) were the key to reversing desertification in the main stream of the Tarim River over the past 30 years.We also explored whether policies necessarily play a positive role in combating and preventing desertification. Based on this, we suggest actively engaging in interdisciplinary research and linking research outcomes with practical situations to formulate scientifically sound policies and measures for desertification prevention and control.