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Climate change is expected to impact the hydrological regime worldwide, and land use and land cover change may alter the effects of the former in some cases. Secondary growth in deforested and abandoned areas is one of the main consequences of land use and cover changes in Amazonia. Among land uses, the effects of the secondary growth in water availability in large scale basins are not well understood. This work analyzes the potential effects of secondary growth under climate and land use change on water availability and hydropower in the Tocantins basin, in the Legal Amazon region of Brazil, using the MHD-INPE hydrological model driven by different climate scenarios and two future socioeconomic-based potential land use scenarios. The model projects decrease on discharge under climate change scenarios, which further cause the simulated hydropower energy potential to decrease significantly. When only deforestation scenarios are included, the effects of climate change are weakened, but when secondary growth is also considered, the effects of climate change are enhanced. Results suggest that different aspects of environmental change, such as secondary growth, may affect water production and the sectors depending on it.