The large population residing in the northern region of India surrounding Delhi mostly depends on water of River Yamuna, a tributary of mighty Ganga for agriculture, drinking and various religious activities. However, continuous anthropogenic activities mostly due to pollution mediated by rapid urbanization and industrialization has profoundly affected river microflora and their function thus its health. In this study, potential of whole genome metagenomics was exploited to unravel the novel consortia of microbiome and their functional potential in the polluted sediments of the river at Delhi. Analysis of high-quality metagenome data from Illumina NextSeq500 revealed substantial differences in composition of microbiota at different sites dominated by Proteobacteria, Bacteroidetes, Firmicutes, Actinobacteria and Chloroflexi phyla. The presence of highly dominant anaerobic bacteria like, Dechloromonas aromatica (benzene reducing and denitrifying), Rhodopseudomonas palustris (organic matter reducing), Syntrophus aciditrophicus (fatty acid reducing), and Syntrophobacter fumaroxidans (sulfate reducing) in the polluted river Yamuna signifies the impact of unchecked pollution in declining health of the river ecosystem. A decline in abundance of phages were also noticed along the downstream of river Yamuna. Mining of mycobiome reads uncovered plethora of fungal communities (i.e., Nakaseomyces, Aspergillus, Schizosaccharomyces, and Lodderomyces) in the polluted stretches due to the availability of higher organic carbon and total nitrogen (%) could be decoded as promising bioindicators of river trophic status. Pathway analysis through KEGG revealed higher abundance of genes involved in energy metabolism (nitrogen and sulphur), methane metabolism, degradation of xenobiotics (Nitrotoluene, Benzoate and Atrazine), two-component system (atoB, cusA and silA) and membrane transport (ABC transporters). Catalase peroxidase and 4-hydroxybenzoate 3-monooxygenase were the most abundant pollution degrading enzymes in polluted sites of river Yamuna. Overall, our results provide crucial insights into microbial dynamics and their function in response to high pollution and could be insightful to the ongoing remediation strategies to clean river Yamuna.