The Earth system is an integrated, self-regulating system under increasing pressure from anthropogenic transformation. The Earth System Science Partnership (ESSP), which was established by the international global environmental change research programs (i.e., DIVERSITAS, IGBP, IHDP and WCRP) facilitates the study of this system in order to understand how and why it is changing, and to explore the implications of these changes for global and regional sustainability. Crucial to this scientific enterprise are interdisciplinary Joint Projects on carbon, food, water and health. This paper analyses the scientific and institutional evolution of ESSP as a framework for interdisciplinary and integrative research of societal relevance. Case studies on food systems, carbon budgets, water security and biodiversity conservation illustrate how these projects have advanced integrated Earth system knowledge. At the institutional level, we explain the transformation of the ESSP governance and how this has further enabled interdisciplinary research. The lessons learnt from ESSP research can contribute to the development of the next generation of Earth system science for sustainability.