Water is at the core of the most difficult sustainability challenges facing humans in the modern era, involving feedbacks across multiple scales, sectors, and agents.We suggest that a transformative new discipline is necessary to address the many and varied water-related challenges in the Anthropocene. Specifically, we propose socio-hydrology as a use-inspired scientific discipline to focus on understanding, interpretation and scenario development of the flows and stocks in the human-modified water cycle across time and space scales. A key aspect of socio-hydrology is explicit inclusion of two-way feedbacks between human and water systems, which differentiates socio-hydrology from other inter-disciplinary disciplines dealing with water. We illustrate the potential of socio-hydrology through three examples of water sustainability problems, defined as paradoxes, which can only be fully resolved within a new socio-hydrologic framework that encompasses such two-way coupling between human and water systems.