Anaerobic oxidation of methane (AOM) is an important microbiological process mitigating the atmospheric release of methane and is mediated by multiple lineages of anaerobic methanotrophic archaea (ANME). Marine-associated ANME lineages are known to shuttle methane-derived electrons to syntrophic sulphate reducing bacteria, while members of the freshwater-residing Methanoperedenaceae can couple AOM to the direct reduction of nitrate and metal oxides independent of a syntrophic partner. Recently, putative arsenate oxidoreductases were identified in several Methanoperedenaceae metagenome assembled genomes (MAGs), signifying the family’s potential to directly mediate AOM coupled to arsenate reduction (As-AOM). Here, we demonstrate As-AOM to be an alternate respiratory strategy for the type-species of the family, ‘Ca. Methanoperedens nitroreducens’. Bioreactor enrichment cultures of ‘Ca. M. nitroreducens’ were fed arsenate and methane resulting in stoichiometrically-balanced arsenate reduction and methane oxidation, indicating their direct coupling. Metagenomic and metatranscriptomic analysis revealed that genes mediating As-AOM were exclusively expressed by Ca ‘M. nitroreducens’, including two putative arsenate reductase operons which were significantly upregulated only in the presence of arsenate. Heterologous gene expression and functional characterisation of the two complexes confirmed their ability to reduce arsenate in vitro. Moreover, comparative genomics of Methanoperedenaceae MAGs recovered from globally distributed arsenic-contaminated environments showed that these arsenate reductase operons are widespread across the family. Collectively, this study highlights As-AOM as a naturally occurring global methane sink and a route for arsenic mobilisation in freshwater sites.