Water resources management, in particular flood control, in the Lancang-Mekong River Basin (LMRB) faces two key challenges in the 21st century: climate change and dam construction. A large-scale distributed Geomorphology-Based Hydrological Model coupled with a simple reservoir regulation model (GBHM-LMK-SOP) is used to investigate the relative effects of climate change and dam construction on the flood characteristics in the LMRB. Results suggest an increase in both flood magnitude and frequency under climate change, which is more severe in the upstream basin and increases over time. However, stream regulation by dam reduces flood risk consistently throughout this century, with more obvious effects in the upstream basin where larger reservoirs will be located. The flood mitigation effect of dam regulation dominates over the flood intensification effect of climate change before 2060, but the latter emerges more prominently after 2060 and dominates the flood risk especially in the lower basin.