We analyzed the distribution and ecology of large gastropods inhabiting the continental shelf of Uruguay and the Río de la Plata estuary, in depths ranging from 4 to 62 m. Seven species belonging to Tonnidae, Ranellidae, Muricidae, Nassariidae, and Volutidae were collected. While the seven species recorded in this study have been previously reported for the Uruguayan coast, here we provide the first detailed description of its habitat preferences in terms of depth, salinity, and sea bottom temperatures. Clustering analysis of stations based on biological data (presence/ absence of species) indicated a spatial segregation of the large gastropods assemblages in three areas: estuarine, low specific richness, dominated by Rapana venosa; inshore (10 to 36 m), high richness, codominated by Zidona dufresnei and Pachycymbiola brasiliana; and offshore (21 to 62 m), intermediate richness, characterized by Z. dufresnei. Mean values for environmental parameters showed significant differences among clusters of stations. Direct developers were more ubiquitous than planktotrophic developers. On the other hand, the exotic planktotrophic species R. venosa dominated the estuarine area. This pattern is not coincident with predictions based on life history traits, such as dispersal capabilities; this suggests that generalizations in this respect are complicated and scale and species dependent.