The aim of this study was to assess the impact of WWTP effluents on the sediment microbial communities throughout the Mureș River. This study shows the existence of an ecological equilibrium between the WWTP effluent disruptors and the resilience of the Mureș River sediment microbiomes, a fact that suggests the river’s stable/balanced ecological status in this regard, partly due to the microbial communities’ resilience to the local impact of WWTP effluents. High-throughput 16S bacterial metabarcoding was used to evaluate the bacterial communities in the sediment. Due to the lotic system’s sediment microbial communities’ sensitivity to environmental changes, we assumed the dependency of these community structures and functions on environmental abiotic and abiotic parameters. The study results show that, although bacterial communities are equally diverse in the three locations (upstream WWTP, WWTP effluents, and downstream WWTP), there is a difference in community structure between the upstream samples and the WWTP samples, while the downstream samples contain a mixture of the upstream and WWTP effluent communities. Just downstream of the WWTP sediment, microbial communities are influenced by the specific input from the WWTP effluents; nevertheless, the river sediment microbiome is resilient and able to further recover its natural microbial composition, as evidenced by the similarity in bacterial community structures at all upstream river locations. This study demonstrates the ecological equilibrium between the WWTP effluent disruptors and the resilience capacity of the Mureș River sediment microbiomes, a fact that indicates the river’s stable/balanced ecological status, in part due to the microbial communities’ resilience to the local impact of WWTP effluents. Based on these findings, a monitoring system should be implemented here in the future.