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Water resources play a vital role in ecosystem stability, human survival, and social development in drylands. Human activities, such as afforestation and irrigation, have had a large impact on the water cycle and vegetation in drylands over recent years. The Badain Jaran Desert (BJD) is one of the driest regions in China with increasing human activities, yet the connection between human management and the ecohydrology of this area remains largely unclear. In this study, we firstly investigated the ecohydrological dynamics and their relationship across different spatial scales over the BJD, using multi-source observational data from 2001 to 2014, including: total water storage anomaly (TWSA) from Gravity Recovery and Climate Experiment (GRACE), normalized difference vegetation index (NDVI) from Moderate Resolution Imaging Spectroradiometer (MODIS), lake extent from Landsat, and precipitation from in situ meteorological stations. We further studied the response of the local hydrological conditions to large scale vegetation and climatic dynamics, also conducting a change analysis of water levels over four selected lakes within the BJD region from 2011. To normalize the effect of inter-annual variations of precipitation on vegetation, we also employed a relationship between annual average NDVI and annual precipitation, or modified rain-use efficiency, termed the RUEmo. A focus of this study is to understand the impact of the increasing planted vegetation on local ecohydrological systems over the BJD region. Results showed that vegetation increases were largely found to be confined to the areas intensely influenced by human activities, such as croplands and urban areas. With precipitation patterns remaining stable during the study period, there was a significant increasing trend in vegetation greenness per unit of rainfall, or RUEmo over the BJD, while at the same time, total water storage as measured by satellites has been continually decreasing since 2003. This suggested that the increased trend in vegetation and apparent increase in RUEmo can be attributed to the extraction of ground water for human-planted irrigated vegetation. In the hinterland of the BJD, we identified human-planted vegetation around the lakes using MODIS observations and field investigations. Four lake basins were chosen to validate the relationship between lake levels and planted vegetation. Our results indicated that increasing human-planted vegetation significantly increased the water loss over the BJD region. This study highlights the value of combining observational data from space-borne sensors and ground instruments to monitor the ecohydrological dynamics and the impact of human activities on water resources and ecosystems over the drylands.