Big Soda Lake, Nevada, is a multi‐extreme meromictic lake, whose hypersaline hyperalkaline bottom waters feature permanent anoxia and high concentrations of arsenic, sulphide and ammonia. These properties make Big Soda Lake—and the adjacent Little Soda Lake—a fascinating system for exploring life's boundaries, discovering novel microbial taxa and identifying biotechnologically useful strains. To date, the taxonomic diversity and metabolic capabilities of microorganisms in this system remain largely unknown. Here, we fill this gap using microbiome surveys across the Big and Little Soda Lake water columns, including 16S rRNA sequencing, fungal ITS2 sequencing and gene‐ and genome‐resolved metagenomics. We accompany these surveys with measurements of salinity, pH, temperature, oxygen, ammonium and ammonia concentrations. Our analyses reveal rich bacterial communities, taxonomically and functionally differentiated along Big Soda Lake's oxycline and, to lesser extent, between lakes. Fungal communities were dominated by a small number of families, while nearly no archaea were detected. Pathways related to perchlorate reduction, anoxygenic phototrophy, fermentation, dissimilatory metabolism of arsenite/arsenate, sulphur compounds, nitrogen compounds and hydrogen, were particularly prevalent. A total of 129 high‐quality bacterial and archaeal metagenome‐assembled genomes (completeness ≥ 80%, contamination ≤ 5%) were recovered, yielding insight into the taxonomic distribution of microbial metabolic pathways.