The Corbulidae are one of a handful of a primarily marine bivalve clades that exhibit a remarkable radiation, marked by increased species richness and divergent morphologies, within a long-lived lake. For corbulids, this diversification occurred within the lower to middle Miocene Pebas Formation of western Amazonia. Only one taxon associated with this radiation (Anticorbula) remains extant. We conducted a series of phylogenetic analyses to characterize diversification of Corbulidae within the Pebas Formation and relate that diversification to geologically older freshwater corbulids from the Paleocene Fort Union Formation of the northern Great Plains (United States). We used these results, as well as a quantitative examination of morphospace occupation, to infer whether Pebasian corbulids represent a true species flock, and whether the lacustrine system represented by the Pebas Formation represents a cradle of, or reservoir for, freshwater corbulid diversity. We conducted two sets of phylogenetic analyses using shell morphology characters. A genus-level data set incorporated type species of freshwater corbulid genera, any Paleocene representatives of these genera, and selected brackish and marine corbulid genera. A species-level analysis added all described freshwater corbulid taxa to the genus-level matrix. Our results were highly resolved (few most-parsimonious trees), but not particularly robust (low branch support). For the genus-level matrix, we used a taxon jackknife procedure to explore the effects of taxon sampling on tree stability and topology. Jackknife results recover a subclade of freshwater taxa (including both Anticorbula and Pachydon species and the Paleocene Ostomya sp.) in 92.4% of trees, although placement of this subclade across the ingroup varies, as do the topologic positions of other freshwater species. Freshwater and marine corbulids also are morphologically distinct from each other, a factor that likely reduced the robustness of our phylogenetic results. By combining these results with paleoecologic, stratigraphic, and morphologic data, we infer that freshwater corbulids arose once within the family, prior to the Cenozoic, with three distinct freshwater lineages present at their first appearance in the late Paleocene of North America. Within the Miocene Pebas system of South America, we reconstruct supralimital morphologic evolution within three lineages as freshwater taxa became variously adapted to the fluid, dysoxic muds characterizing lake-bottom facies representative of the Pebas lacustrine system. In addition, corbulids apparently successfully coped with high predation pressures from co-occurring shell-crushing predators. Finally, we consider that freshwater Corbulidae were primarily fluvial taxa throughout their geologic history, with a relatively ephemeral radiation within the Pebasian lake system, thus making the Pebasian system a cradle of diversity for several corbulid lineages.