Non-native species have been introduced at escalating rates during the last decades, mainly due to the dispersion generated by the increasing trade and transport worldwide. Mollusks, the second largest metazoan phylum in terms of species richness, are no exception to this pattern, but, to date, a comprehensive synthesis of non-native mollusk species (NNMS) in South America was not available. For this purpose, an e-discussion group was formed with malacologists and taxonomists from South America, where we exchanged and analyzed bibliography, databases and information about NNMS, providing expert opinion to this assessment. The first list of non-native mollusk species for South America, considering terrestrial, freshwater and marine environments, includes 86 NNMS distributed in 152 ecoregions (terrestrial, freshwater and marine) of the 189 recognized for the South American continent. Information on their native region, vectors, first record for South America and distribution, are also provided. In the analysis of the distribution of the NNMS and the entry points of each species (e.g., ports, cargo and passenger airports, cities) and status of conservation of the ecoregions, four hot spots were recognized: Subtropical-Atlantic, Northern Andes, Central Andes and Southern Andes. This work, thus, sets the baseline on NNMS for South America, a key piece of information regarding the development of policies targeting the management of biological invasions and their socio-ecological impacts.