World leaders at the 2015 United Nations Sustainable Development Summit in New York have re- confirmed the relevance of sustainability as the guiding paradigm in countering the development and climate crisis of the Anthropocene. Recent decades however, have been characterized by confusion, contestations, and arbitrariness in defining the nature and pathways of sustainable development. Humanity must urgently find ways to unlock the potential of the sustainability paradigm and organize a sustainability transforma- tion. An emerging sustainability science community has already established considerable consensus on essential features of transformative science and research. Sustainability scholars are providing growing evidence that an emancipatory and democratic construction of sustainable... development and more equitable, deliberative, and democratized knowledge generation are pivotal in tackling sustainability challenges. These findings are further underpinned by experiences gained in the Eastern and Southern Africa Partnership Programme (1999–2015)—a rare case of a long-term, transnational, and transdisciplinary research en- deavour already completed. The programme fulfilled the dual role which is compulsory in transformative research: It generated contextualized knowledge and innovation at the science–society interface while simultaneously securing meaningful participation and Southern agency in a co-evolutionary process. This paper offers insight into the programme’s adaptive structure and implementation processes, which fostered deliberation, capacity development, and joint programme navigation benchmarked against local needs and broader sustainability demands. The ESAPP experience confirms that, if taken as the overarching frame of reference for all actors involved, the sustainability paradigm unfolds its integrative and transformative power. It enables sustainability-oriented actors from all scientific and practical fields to seek consilience between differing development and innovation paradigms and synchronize their development agendas and research frameworks on behalf of societal co-production of knowledge and innovation. Accordingly, the sustainability paradigm has the power to guide development and innovation policy, and practice out of the current confusion and ineffectiveness.