Understanding the spatiotemporal distribution of climate extremes at the river basin scale is crucial for sustainable water resource management, especially under changing climate conditions. In Ghana’s Pra River Basin, where livelihoods are tightly linked to climate variability, shifts in extreme rainfall and temperature events can have significant socioeconomic impacts. This study assesses historical and projected changes in climate extremes using thirteen WMO-recommended rainfall and temperature extreme indices. Simulations from four CORDEX-Africa regional climate models under RCP4.5 and RCP8.5 scenarios were analysed for three future periods: near-term (2026–2045), mid-century (2046–2065), and late-century (2066–2100), relative to a 1991–2020 baseline. Historical trends were derived from high-resolution historical data developed under the Building Climate-resilience into Basin Water Management (CREAM) project. Findings show marked increases in extreme rainfall indices in recent decades, particularly between 2011 and 2020. Temperature extremes also reveal consistent warming, with more frequent warm days and nights and fewer cold events. While most rainfall indices exhibited significant trends, changes in consecutive dry days and moderate rainfall frequency were not statistically significant. Notably, very intense rainfall events have doubled over the last decade. Projections indicate these trends will persist, heightening risks to water security, agriculture, health, and ecosystems. The study highlights the urgent need to revise and implement Integrated Water Resources Management (IWRM) strategies in the Pra Basin to adapt to increasing climate extremes and enhance resilience across sectors.