Populus euphratica (P. euphratica) is a dominant tree species in the arid and semi-arid regions along the main stem of the Tarim River. This study aims to explore the response of microbial communities in the rhizosphere soil of P. euphratica to varying groundwater depths (GWD) and to elucidate the ecological functions of key microbial groups in drought resistance. We established three groundwater depth levels (3.8 m, 5.4 m, and 7.35 m) and employed metagenomic sequencing technology to systematically analyze the topological characteristics of functional microbial community networks, as well as the types and quantities of key microbial groups in the rhizosphere soil of P. euphratica under different GWD conditions. The results indicate that compared to GWDs of 3.8 m and 7.35 m, the average degree and graph density of microbial communities in the rhizosphere soil of P. euphratica at a depth of 5.4 m are the highest. This suggests that at a GWD of 5.4 m, the connectivity and stability of the microbial network structure in the rhizosphere soil of P. euphratica are significantly enhanced. Analysis of the Zi-Pi values within the microbial network structure reveals that, compared to GWDs of 3.8 m and 7.35 m, a depth of 5.4 m supports the greatest variety and quantity of key microbial species in the rhizosphere soil of P. euphratica. The four connecting nodes identified are Actinophytocola, Haladaptatus, Devosia and Pseudonocardia. Spearman correlation analysis demonstrates that the relative abundance of the key bacterial genus Mesorhizobium in the rhizosphere soil of P. euphratica at different GWD is significantly positively correlated with soil catalase (CAT) and urease (UE) activity. Furthermore, the relative abundance of the key bacterial genus Pseudonocardia shows a significant positive correlation with soil total nitrogen (TN) and ammonium nitrogen (NH4+-N) (p < 0.05). The relative abundance of the key bacterial genus Devosia exhibits a highly significant positive correlation with soil water content (SWC) (p < 0.01) and a significant negative correlation with soil NH4+-N (p < 0.05). Additionally, the relative abundance of Devosia is significantly positively correlated with soil CAT (p < 0.05). This study provides a theoretical foundation for the conservation of desert poplar forests in arid regions and for the identification and cultivation of specific key microbial communities in the rhizosphere soil of P. euphratica.