Blue mussels (Mytilus edulis) are among the most consumed fishery products globally. Foodborne outbreaks of mussel-associated infections by viral, bacterial, and parasitic pathogens have been reported in the last years. In this study, we investigated the occurrence, genetic diversity, and zoonotic potential of the diarrhea-causing enteric protozoan Giardia duodenalis in blue mussels from Caleta Co´rdova in Chubut Province, southeast Patagonia, Argentina. A total of 344 free-living blue mussels were collected and distributed in 53 aliquots of pooled mussel tissue (each containing 5–7 specimens) during the period 2015–2018. Conventional optical microscopy was used as screening method for the detection of G. duodenalis cysts in pooled, homogenized tissues. Samples with a positive result were assessed by a multilocus sequence genotyping scheme based on the amplification of partial fragments of the glutamate dehydrogenase and b-giardin genes of the parasite. G. duodenalis cysts were found in 30.2% (16/53) of the aliquots of pooled mussel tissue tested. PCR and sequencing analyses revealed the presence of G. duodenalis subassemblage BIV in selected aliquots. To the best of our knowledge, this is the first description of zoonotic subassemblage BIV from blue mussels in Argentina.