The mortality and economic losses caused by floods are increasing. In fact, the top 10 costliest floods since 1900 are all occurred over the past thirty years. On the one hand, this is the result of economy development, but on the other hand the hydrological cycle was largely intensified by climate change and human activities, particularly land use change. Disentangling these effects on flood risk change is very challenging due to the compound nature of the driving factors. Using the best available long-term historical climate forcing and a land surface model that is capable of representing the hydrological effects of land use, here we attempted to compare the effects on flood risk between climate change and land use. Results showed that over the past 110 years, climate change’s effects were mixed, strong, and widespread, while land use’s contributions were dominantly increase, modest, and restricted to the areas with large land use changes. However, when we aggregated their effects over large regions (e.g., major river basins), flood risk increase from land use may surpass that from climate change, as climate change’s effects offset from locations to locations within regions. This suggests that we have to reduce large-scale deforestation to avoid the catastrophic consequence of floods from the compounding effects of climate change and large-scale deforestation.