The first successful sand-control was achieved in the Mu Us Desert by local people in the 1950–1960s, and their experience and approach have been extended to the whole Ordos and Northern China since then. The objective of this paper is to assess comprehensively the effectiveness of sand-control in 15 counties in and around Mu Us using multitemporal satellite images and socioeconomic data. After atmospheric correction, Landsat TM and OLI images were harnessed for land cover classification based on the ground-truth data and for derivation of the GDVI (generalized difference vegetation index) to extract the biophysical changes of the managed desert and desertification. Climatic, socioeconomic, environmental and spatial factors were selected for coupling analysis by multiple linear and logistic regression models to reveal the driving forces of desertification and their spatial determinants. The results show that from 1991 to 2020, 8712 km2 or 63% of the desert has been converted into pastures and shrublands with a greenness increase of 0.3509 in GDVI; the effectiveness of sand-control is favored by the rational agropastoral activities and policies; though desertification occurs locally, it is associated with both climatic and socioeconomic factors, such as wind speed, precipitation, water availability, distance to roads and animal husbandry.