Abstract: The adequacy of freshwater resources remains a critical challenge for a sustainable and growing society. We present a self-consistent risk-based assessment of water availability and use under future climate change and socioeconomic growth by midcentury across southern and eastern Asia (SEA). We employ large ensemble scenarios from an integrated modeling framework that are consistent across the spectrum of regional climate, population, and economic projections. We find socioeconomic growth contributes to an increase in water stress across the entire ensemble. However, climate change drives the ensemble central tendency toward an increase in water stress in China but a reduction in India, with a considerable spread across the ensemble. Nevertheless, the most deleterious unabated climate-change impact is a low probability but salient extreme increase in water stress over China and India. In these outcomes, annual withdrawals will routinely exceed water-storage capacity. A modest greenhouse gas mitigation pathway eliminates the likelihood of these extreme outcomes and also benefits hundreds of millions of people at risk to various levels of water stress increase. Over SEA we estimate an additional 200 million people under threat of facing at least heavily water-stressed conditions from climate change and socioeconomic growth, but the mitigation scenario reduces the additional population-under-threat by 30% (60 million). Nevertheless, there remains a 1-in-2 chance that 100 million people across SEA experience a 50% increase in water stress and a 1-in-10 chance they experience a doubling of water stress. Therefore, widespread adaptive measures may be required over the coming decades to meet these unavoidable risks in water shortfalls.