Mine inflow threats mine safety production underground, and may trigger a decline in the groundwater level in the mine area, causing irreversible successional degradation of surface vegetation. In view of the key problems such as inaccurate generalization of boundary conditions and unreliable selection of hydrogeological parameters when constructing numerical models of water inflow, this study aims to accurately predict mine water inflow, ensure the safe mining of coal seams, and provide theoretical and data support for the protection of desert vegetation in the study area. The natural boundary is selected as the perimeter of the research area, and the model is repeatedly revised on the basis of fully collecting and analyzing the data of drilling, geophysical prospecting, pumping test, groundwater long-term monitering, and the scope of the mine goaf and its water inflow, and thus a more realistic three-dimensional unstable flow numerical model of groundwater is constructed. In addition, the model simulation and identification are carried out according to the expansion process of the mine goaf and its water inflow and groundwater monitoring data, which demonstrates the rationality and reliability of the model. The established numerical model is used to predict the mine inflow and submersible level depth drop under coal seam mining conditions, and then the influence of diving level decline on desert vegetation is analyzed based on the relationship between diving depth and desert vegetation. The results show that the predicted water inflow in the mine is 3.08×104 m3/d, resulting in a decrease of 2.08−2.35 m in the diving level in the mine area, which will lead to the deterioration or even partial withering of the representative vegetation sand willow and poplar in the mine area, showing a succession trend from mesophytic vegetation type to xerophytic vegetation. The results can provide more accurate water inflow prediction in the study area, scientific and effective measures for the protection of desert vegetation in mining areas, and reliable treatment ideas for the construction of similar numerical models of groundwater flow.