A quantitative understanding of changes in water resources is crucial for local governments to enable timely decision-making to maintain water security. Here, we quantified natural-and human-induced influences on the terrestrial water storage change (TWSC) in Sichuan, Southwest China, with intensive water consumption and climate variability, based on the data from the Gravity Recovery and Climate Experiment (GRACE) and its Follow-on (GRACE-FO) during 2003–2020. We combined the TWSC estimates derived from six GRACE/GRACE-FO solutions based on the uncertainties of each solution estimated from the generalized three-cornered hat method. Metrics of correlation coefficient and contribution rate (CR) were used to evaluate the influence of precipitation, evapotranspiration, runoff, reservoir storage, and total water consumption on TWSC in the entire region and its five economic regions. The results showed that a significant improvement in the fused TWSC was found compared to those derived from a single model. The increase in regional water storage with a rate of 3.83 ± 0.54 mm/a was more influenced by natural factors (CR was 53.17%) compared to human influence (CR was 46.83%). Among the factors, the contribution of reservoir storage was the largest (CR was 42.32%) due to the rapid increase in hydropower stations, followed by precipitation (CR was 35.16%), evapotranspiration (CR was 15.86%), total water consumption (CR was 4.51%), and runoff (CR was 2.15%). Among the five economic regions, natural influence on Chengdu Plain was the highest (CR was 48.21%), while human influence in Northwest Sichuan was the largest (CR was 61.37%). The highest CR of reservoir storage to TWSC was in Northwest Sichuan (61.11%), while the highest CRs of precipitation (35.16%) and evapotranspiration (15.86%) were both in PanXi region. The results suggest that TWSC in Sichuan is affected by natural factors and intense human activities, in particular, the effect of reservoir storage on TWSC is very significant. Our study results can provide beneficial help for the management and assessment of regional water resources.