Monitoring variations in terrestrial water storage (TWS) is of great significance for the management of water resources. However, it remains a challenge to continuously monitor TWS variations using in situ observations and hydrological models because of a limited number of gauge stations and the complicated spatial distribution characteristics of TWS. In contrast, the Gravity Recovery and Climate Experiment (GRACE) could overcome the aforementioned restrictions, providing a new reliable means of observing TWS variation. Thus, GRACE was employed to investigate TWS variations in Northwest China (NWC) between April 2002 and March 2016. Unlike previous studies, we focused on the interactions of multiple climatic and vegetational factors, and their combined effects on TWS variation. In addition, we also analyzed the relationship between TWS variations and socioeconomic water consumption. The results indicated that (i) TWS had obvious seasonal variations in NWC, and showed significant decreasing trends in most parts of NWC at the 95% confidence level; (ii) decreasing sunshine duration and wind speed resulted in an increase in TWS in Qinghai province, whereas the increasing air temperature, ameliorative vegetational coverage, and excessive groundwater withdrawal jointly led to a decrease in TWS in the other provinces of NWC; (iii) TWS variations in NWC had a good correlation with water storage variations in cascade reservoirs of the upper Yellow River; and (iv) the overall interactions between multiple climatic and vegetational factors were obvious, and the strong effects of some climatic and vegetational factors could mask the weak influences of other factors in TWS variations in NWC. Hence, it is necessary to focus on the interactions of multiple factors and their combined effects on TWS variations when exploring the causes of TWS variations.