Large-scale ecological restoration (ER) projects have been implemented in northwest China in recent decades as a means to prevent desertification and improve ecosystem services. However, previous studies have demonstrated adverse impacts in the form of widespread soil water deficit caused by intensive ER activities. Understanding the role of climate change and ER efforts in vegetation dynamics and soil moisture consumption is essential for sustainable ecosystem management. Here, we used the break for additive season and trend (BFAST) method to analyse spatial patterns in the normalized difference vegetation index (NDVI) variation over the agro-pastoral ecotone of northwest China (APENC) for 2000–2015. From the combined use of generalized additive modelling (GAM) and residual-trend analysis (RESTREND), we distinguished and quantified the effects of climate and human management on vegetation and soil water dynamics. Approximately 78% of the area showed vegetation variations representing a significant change in NDVI, of which more than 68% were categorized as abrupt changes. Large areas of the abrupt change type, interrupted increase and monotonic increase in NDVI were observed before 2006, and small areas of the change type of negative reversals were observed after 2012. Anthropogenic activity was found to be the major driving factor of variation in vegetation (contribution rate of 56%) and soil moisture (contribution rate of 78%). The vegetation expansion, which was mainly related to the large number of ER programs that started in 2000, was found to increase soil moisture depletion. By comparing areas where anthropogenic activities had a high contribution rate to vegetation increase and areas where soil moisture consumption was severely increased, we identify and discuss hotspot areas of soil moisture consumption caused by the ER programs. The current methodological workflow and results represent a novel foundation to inform and support water resource management and ecological-restoration-related policy making.