In countries where severe drought is an anticipated effect of climate change and in those that heavily depend on upstream nations for fresh water, the effect of drier conditions and consequent changes in the transboundary streamflow regime induced by anthropogenic interventions and disasters leads to uncertainty in regional water security. As a case in point, we analyze Jordan's surface water resources and agricultural water demand through 2100, considering the combined impacts of climate change and land-use change driven by the Syrian conflict. We use bias-corrected regional climate simulations as input to high-resolution hydrologic models to assess three drought types: meteorological (rainfall decrease), agricultural (soil moisture deficit), and hydrologic (streamflow decline) under future scenarios. The historical baseline period (1981-2010) is compared to the future (2011-2100), divided into three 30-year periods. Comparing the baseline period to 2070-2100, average temperature increases by 4.5°C, rainfall decreases by 30%, and multiple drought-type occurrences increase from ~8 in 30 years to ~25 in 30 years. There is a significant increase in the contemporaneous occurrence of multiple drought types along with an 80% increase in simultaneous warm and dry events. Watershed simulations of future transboundary Yarmouk-Jordan River flow from Syria show that Jordan would receive 51 to 75% less Yarmouk water compared to historical flow. Recovery of Syrian irrigated agriculture to pre-conflict conditions would produce twice the decline in transboundary flow as that due to climate change. In Jordan, the confluence of limited water supply, future drought, and transboundary hydrologic impacts of land use severely challenges achieving freshwater sustainability.