The complex relationships within the water-energy-food security nexus tend to be place-specific, increasing the importance of identifying transferable principles to facilitate implementation of a nexus approach. This paper aims to contribute transferable principles by using global model data and concepts to illustrate and analyze the water history of Central Asia. This approach builds on extensive literature about Central Asia and global change as well as recent advances in global water modeling. Decadal water availability and sectorial water consumption time series are presented for the whole 20th century, along with monthly changes in discharge attributable to human influences. Concepts from resilience and socio-ecological system theory are used to interpret the results and identify five principles relevant to managing the transboundary nexus: (1) the subsystems included/excluded from the nexus are case-specific and should be consciously scrutinized; (2) consensus is needed on what boundaries can acceptably be crossed within the nexus; (3) there is a need to understand how reducing trade-offs will modify system dependencies; (4) global stakeholders have both a responsibility and right to contribute to the shaping of the nexus; (5) combining data with global and local perspectives can help to enhance transferability and understanding of shared problems in our globalized world.