The uncertainties in soil erosion (SE) are further intensified by various factors, such as global warming, regional warming and humidification, and vegetation cover changes. Moreover, quantitative evaluations of SE in major basins of Central Asia (CA) under changing environments have rarely been conducted. This study conducted quantitative evaluation of SE in four major basins (Syr Darya Basin (SDB), Amu Darya Basin (ADB), Ili River Basin (IRB) and Tarim River Basin (TRB) using the Revised Universal Soil Loss Equation (RUSLE) and analyzed the main driving factors. SE quantities in the basins presented relatively consistent upward fluctuating trends from 1982 to 2017. Vegetation cover variation fluctuated significantly from 1982 to 2017. Specifically, vegetation cover decreased continuously in SDB, ADB, and IRB, but increased gradually in TRB. Pixels with positive spatial variation of vegetation mainly occurred around lakes and oases near rivers. The Normalized Difference Vegetation Index (NDVI) showed higher correlation with precipitation (80.5%) than with temperature (48.3%). During the study period, the area of arable land (AL) exhibited the largest change among all land use types in CA. Under long-term human activities, the proportion of NDVI of other land types converting to AL was the highest. In the structural equation model (SEM), precipitation, temperature, Shannon Diversity Index (SHDI), and NDVI strongly influenced SE. Overall, the major basins in CA were jointly affected by climate, human activities, and vegetation. Specifically, climatic factors exerted the strongest influence, followed by SHDI (human activities). SE was found to be relatively serious in ADB, SDB, and IRB, with SE in SDB even approaching that in the Loess Plateau. Under the background of global changes, appropriate water and land resource management and optimization configurations should be implemented in CA with reference to TRB in order to relieve local SE problems.