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Large-scale spatial and temporal variability in environmental conditions may result in differences in life-history traits, population demography, and abundance of sandy-beach species. We analyzed the effects of salinity, chlorophylla(chla), and sea surface temperature (SST) on population parameters of the wedge clamDonax hanleyanusfrom 75 South American sandy beaches covering a 15° latitudinal range. Generalized modeling results showed that between-beach differences in abundance, population structure, growth performance, productivity, mortality, and individual shell mass were mainly explained by salinity fluctuations, with chlaand SST as secondary contributors, overriding, in most cases, local habitat features (Dean’s parameter, grain size, slope). Our results provide valuable insights into macroscale ecological processes, setting a basis to delineate conservation guidelines at large spatial scales that respond to the potential effects of climate variability and change on sandy beach populations.