The spatio-temporal pattern changes between water resources and vegetation growth, and their coupling relationship have always been important issues in hydrology and ecology. This case study of Shule River Basin, which is a typical inland river basin in an arid area, investigated the spatio-temporal pattern changes in water resources and vegetation growth, and their coupling relationship. The terrestrial water storage anomaly (TWSA) inversed by the GRACE satellite was used along with the enhanced vegetation index (EVI) derived from the MODIS data for 2002 to 2016. The results indicate that (1) on a temporal scale, the TWSA and EVI of the basin show obvious periodicity, seasonality, and tendency; (2) on a spatial scale, the TWSA and EVI of the basin, based on grid cell size, show obvious spatial heterogeneity at the whole basin and sub-regional scales; (3) the coupling relationship analysis shows that there is a moderately negative correlation between annual average TWSA and the EVI across the whole basin and that there is a highly negative correlation in the central plain area. However, there is no significant correlation in the southern mountainous area and the northern mountainous area. The proportions of grid cells that have a highly negative correlation, a moderately negative correlation, and a low negative correlation between the TWSA and EVI are 19%, 32%, and 31% of the total, respectively. Only 18% show a low positive correlation. Therefore, the coupling relationships between annual average TWSA and EVI are complex and show the clear spatial heterogeneity and scale effects in the basin. The research conclusions could help optimize the allocation and rational utilization of water resources and ecologically sustainable development in the Shule River Basin and the arid regions of China.