The Pantanal, the world’s largest tropical wetland, dried unusually over 2000-2021, with climate variability and land clearing in its headwaters both proposed as causes. Land-cover maps, gauged discharge and records of rainfall and evaporative demand back to 1951 were combined in a water balance analysis for the Upper Paraguay River Basin, reaching three decades further back than the land-cover record. We found that the runoff change across two wet and two dry periods, 96% traced to climate and only 4% to land cover, while wetland area shrank about 30% after 1985. The recent dry period was hotter and more arid than the 1965-1975 drought and may worsen rather than revert to humid conditions.