Recognized globally as an ecologically fragile area, the Arid Zone of Central Asia (ACA) exhibits vegetation that is highly responsive to climate change and human activities. Elucidating the individual and combined impacts of climate, soil, topography, and human activities on vegetation, as well as pinpointing key growth factors, is essential for regional ecological conservation and rehabilitation. This study, based on the remote sensing data, Theil-Sen median and Mann-Kendall trend analysis and test methods were used to evaluate the spatio-temporal dynamics of vegetation from 2001 to 2020, combined with the coefficient of variation, and quantified the main factors of spatial and temporal variation of vegetation using Geographical Detector and partial correlation analysis to assess suitable habitats for vegetation. The study's findings are as follows: (1) Across the two decades, the NDVI in the ACA exhibited a modest upward trend (0.00005/10a), with 57.3% of areas witnessing enhanced vegetation conditions. Overall, NDVI values for vegetation were lowest in 2008 and highest in 2016. Over the past two decades, changes in vegetation have shown a periodic fluctuation pattern characterized by a cycle of decline, increase and subsequent decline. The Northern Steppes of Central Asia (NSCA) have shown significant inter-annual variations in vegetation, with less stability in the west-central part of the ACA and relative stability in other regions. (2) Regarding the spatial variation in vegetation, natural factors have a greater impact on vegetation than human factors, precipitation, Volumetric Water Content (VWC), soil classification, and vegetation categorization possess substantial explanatory power. The interactions among these factors are either synergistically enhancing or nonlinearly reinforcing, with the most pronounced interaction occurring between land use change and slope aspect. (3) Vegetation exhibits a predominantly positive correlation with VWC and climatic factors, and vegetation is more sensitive to VWC than to precipitation and air temperature. VWC is identified as the primary driver of vegetation change across 43.8% of the region, serving as the dominant factor in promoting vegetation growth across various ecological zones. In addition, the area influenced by the dominance of temperature is 17.5%, exceeding that of precipitation (15.9%) and SPEI (11.8%). Furthermore, the modest negative correlation between population density and vegetation is not substantial, indicating that the detrimental impact of human activities on vegetation is constrained. In vegetation restoration strategies, grasslands, croplands, and mixed forests are identified as suitable vegetation types that can contribute to ecological stability and sustainable land use. This study provides a scientific basis for vegetation restoration and management, guiding the selection of appropriate vegetation types under the influence of natural factors and human activities.