Many regions in Africa and the Middle East are vulnerable to drought and to water and food insecurity, motivating agency efforts such as the U.S. Agency for International Development’s (USAID) Famine Early Warning System Network (FEWS NET) to provide early warning of drought events in the region. Each year these warnings guide life-saving assistance that reaches millions of people. A new NASA multi-model, remote sensing-based hydrological forecasting and analysis system, NHyFAS, has been developed to support such efforts by improving the FEWS NET’s current early warning capabilities. NHyFAS derives its skill from two sources: (i) accurate initial conditions, as produced by an offline land modeling system through the application and/or assimilation of various satellite data (precipitation, soil moisture, and terrestrial water storage); and (ii) meteorological forcing data during the forecast period as produced by a state-of-the-art ocean-land-atmosphere forecast system. The land modeling framework used is the Land Information System (LIS), which employs a suite of land surface models, allowing multi-model ensembles and multiple data assimilation strategies to better estimate land surface conditions. An evaluation of NHyFAS shows that its one-to-five month forecasts successfully capture known historic drought events. The system also benefits from strong collaboration with end-user partners in Africa and the Middle East, who provide insights on strategies to formulate and communicate early warning indicators to water and food security communities. The additional lead time provided by this system will increase the speed, accuracy and efficacy of humanitarian disaster relief, helping to save lives and livelihoods.