Mining is one of the main pollution issues worldwide, causing the greatest disturbances to the environment. Industrial and artisanal mining activities are widespread in Mexico, being a major global producer of various metals. This study aimed to assess the ecological impairments resulting from mining activities using the aquatic macroinvertebrates assemblages (MA). A multiple co-inertia analysis (MCOA) was applied to determine the relationships between environmental factors, habitat quality, heavy metals, and aquatic macroinvertebrates in two rivers of the Central Plateau, Mexico. The results revealed three contrasting environmental conditions and different MA. High concentrations of heavy metals, nutrients, and salinity limit the presence of various families of seemingly sensitive macroinvertebrates, these factors were identified as the drivers of structural changes in the MA, showing that not only mining activities, but also agriculture, and villages in the basin, exert negative effects to the macroinvertebrate communities. Diversity indices showed that the lowest diversity matched with both, the most polluted and the most saline rivers. The rivers studied displayed a high alkalinity and hardness, which can lead to the formation of metal precipitates and thus acting as a protection to aquatic biota. Aquatic biomonitoring in rivers, impacted by mining and other human activities, is critical for detecting the effect of metals and other pollutants to improve management and conservation strategies. This study supports the design of cost-effective and accurate water quality biomonitoring protocols in developing countries.