The Uruguay River basin experienced extensive land use change during the second half of the twentieth century as a result of expansion of agricultural area, while streamflow and precipitation increased during the same period. This study assesses the impact of land use change between 1960 and 2000 on streamflow using a hydrology model that explicitly accounts for the role of land cover. Although the model suggests that land use change could have large effects on streamflow, changes in mean streamflow are attributable to climatic variations and not to land cover change. On the other hand, a faster runoff response to precipitation was observed toward the end of the period, which does appear to be attributable to land cover change. Overall, however, the positive trend observed in the Uruguay River streamflow during the second half of the past century should be attributed to increased precipitation, rather than land cover change.