Many basins in the Cerrado biome already face increases in water disputes caused by agricultural expansion without long-term planning and monitoring of natural resources. The amount and timing of water availability are crucial for the socioeconomic development of agricultural activities and climate change resilience enhancement in the Cerrado. This study relied on a dataset developed for the Cerrado to characterize its climate and current water availability status. Different climate indices and hydrological signatures were adopted to describe the energy and water budget, climate seasonality, flow magnitude, flow dynamics, and average duration of low-flow events. Risk analysis was carried out to classify the monthly risk severity and identify periods and regions under a higher pressure regarding water availability in the Cerrado. Overall, the water availability is higher in the western and southern regions and lower in the eastern and northern regions, which experience a transition to a humid and semiarid climate, respectively. The water resources in the Cerrado occur under the highest pressure in September and October. We also identified regions with the potential to increase sustainable water use. These regions exhibit a low ratio between the flow equal to or exceeded 95% of the time and the mean flow (Q95/Q), which indicates that sustainable water use may be improved with techniques related to flow regularization and rainwater/runoff harvesting.