Abstract: The arid inland river basin in the northwest has undergone large-scale exploitation of soil and water resources, which has had a significant impact on regional groundwater and ecological environment. However, the long-term evolution mechanism of groundwater remains unclear. This study takes the Aksu River Basin in Xinjiang as a typical area. By comparing the latest groundwater monitoring data with historical data, the historical process, characteristics, and genetic pattern of the spatiotemporal changes in groundwater flow field and burial depth in the basin are analyzed. The relationship between the long-term evolution of groundwater in the area and land use changes is explored, and the mechanism of groundwater evolution under the influence of human activities is revealed. The results indicate that since 1979, with the increase of farmland area, the regional groundwater flow field has experienced a historical process from a nearly natural state to a strong impact of human activities. Groundwater have decreased to varying degrees, and the direction of groundwater flow in local areas and the replenishment and discharge relationship with the groundwater have changed. Groundwater mainly relies on lateral runoff supply, but the intensity of manual mining is much greater than that of lateral supply, resulting in a significant decrease in groundwater table. Taking the line from Yingairike Township to Karatale Township in the central part of the research area as the boundary, the decrease in the groundwater table in the northern region was greater than that in the southern region, because land use change causes the change of groundwater recharge and discharge conditions. The groundwater quality in the northern region is good, and it is exploited in large quantities for agricultural irrigation, while in the southern region, surface water is mainly used for irrigation due to poor groundwater quality. The intensity of groundwater extraction is low, so the decline of groundwater in the south is not as obvious as that in the north. The research results can provide scientific basis for sustainable exploitation and ecological protection of groundwater in Aksu river basin and similar areas in Xinjiang.