The accessibility, quantity, and quality of water resources are the basic requirements for guaranteeing water resource security. Research into regional water resource accessibility will contribute to improving regional water resource security and effective water resource management. In this study, we used a water resource accessibility index model considering five spatial factors to evaluate the grid-scale water resource accessibility and constructed the spatial pattern of water resource accessibility in Southwest China. Then, we analyzed the coupling coordination degree between county-level water resource accessibility and eco-socio-economic water demand elements. The water resource accessibility showed obvious regional differences, and the overall trend gradually decreased from Southeast to Northwest. The coupling coordination degree between county-level water resource accessibility and eco-socio-economic water demand elements was between 0.26 and 0.84, and was relatively low overall, whereas the counties (districts) with high coordination, moderate coordination, low coordination, reluctant coordination, and incoordination accounted for 0.92%, 5.31%, 21.06%, 59.71%, and 13.00% of total counties (districts), respectively. Therefore, the Southwest region needs to further strengthen the construction of its agricultural irrigation facilities, protect the water resources, and coordinate the relationship between water resource management and water demand elements to comprehensively guarantee regional sustainable development.