Heavy metal (HMe) pollution in regions with mining and metallurgy activities is known to be a serious environmental problem worldwide. Hydrological processes contribute to the dissemination of HMes (drainage, precipitation, flow rate). The aim of the present study is to investigate the microbial community structure in ten river sediments sampled in different regions of East Kazakhstan, which are contaminated with HMes. The overall degree of sediment contamination with HMes (Cr, Cu, Zn, Pb, and Cd) was assessed using the pollution index Zc, which ranged from 0.43 to 21.6, with the highest in Ridder City (Zc = 21.6) and Ust-Kamenogorsk City, 0.8 km below the dam of the hydroelectric power station (Zc = 19.6). The tested samples considerably differed in organic matter, total carbon, nitrogen, and phosphorus content, as well as in the abundance of HMe-related functional gene families and antibiotic resistance genes. Metagenomic analysis of benthic microorganisms showed the prevalence of Proteobacteria (88.84–97.61%) and Actinobacteria (1.21–5.98%) at the phylum level in all samples. At the class level, Actinobacteria (21.68–57.48%), Betaproteobacteria (19.38–41.17%), and Alphaproteobacteria (10.0–39.78%) were the most common among the classified reads. To the best of our knowledge, this is the first study on the metagenomic characteristics of benthic microbial communities exposed to chronic HMe pressure in different regions of East Kazakhstan.