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Providing reliable estimates of streamflow and hydrological fluxes is a major challenge for water resources management over national and transnational basins in South America. Global hydrological models and land surface models are a possible solution to simulate the terrestrial water cycle at the continental scale, but issues about parameterization and limitations in representing lowland river systems can place constraints on these models to meet local needs. In an attempt to overcome such limitations, we extended a regional, fully coupled hydrologic-hydrodynamic model (MGB; Modelo hidrológico de Grandes Bacias) to the continental domain of South America and assessed its performance using daily river discharge, water levels from independent sources (in situ, satellite altimetry), estimates of terrestrial water storage (TWS) and evapotranspiration (ET) from remote sensing and other available global datasets. In addition, river discharge was compared with outputs from global models acquired through the eartH2Observe project (HTESSEL/CaMa-Flood, LISFLOOD and WaterGAP3), providing the first cross-scale assessment (regional/continental×global models) that makes use of spatially distributed, daily discharge data. A satisfactory representation of discharge and water levels was obtained (Nash-Sutcliffe efficiency, NSE > 0.6 in 55% of the cases) and the continental model was able to capture patterns of seasonality and magnitude of TWS and ET, especially over the largest basins of South America. After the comparison with global models, we found that it is possible to obtain considerable improvement on daily river discharge, even by using current global forcing data, just by combining parameterization and better routing physics based on regional experience. Issues about the potential sources of errors related to both global- and continental-scale modeling are discussed, as well as future directions for improving large-scale model applications in this continent. We hope that our study provides important insights to reduce the gap between global and regional hydrological modeling communities. [ABSTRACT FROM AUTHOR]