Our proposed work assembles an interdisciplinary team of physical and social scientists to improve decadal predictions of decadal-multidecadal drought risk and to make those predictions more useful to decision-makers. We take advantage of multiple resources that provide us with exceptional capabilities to address these issues. We have generated an unprecedented ensemble of model simulations of the past millennium, 20th, and 21st centuries from the state-of-the-art National Center for Atmospheric Research’s (NCAR) Community Earth System Model (CESM). We also utilize an expanding set of published and emerging paleoclimate data from multiple proxies that reveal decadal-multidecadal hydroclimatic variability in our study regions. In addition, a longstanding network of stakeholders and collaborators in the southwest US and Mexico are allowing us to develop best practices in applying drought risk estimates to real-world problems across a broad social context. Our results highlight multiple regions where natural drought variability and anthropogenic change join forces to amplify the risk of prolonged, severe drought: southwestern North America, Australia, Amazonia, and West Africa/Sahel, South Asia, and the Caribbean.