There is an urgent need to address the grand sustainability challenges of our time, and to explore new and more responsible ways of operating, researching, and innovating that enable society to respond to these challenges. The emergent Responsible Research and Innovation (RRI) policy agenda can act as a catalyst towards the development of new and more responsible research and innovation efforts. Inevitably, higher education needs to be closely attuned to this need and agenda, by preparing students to engage in RRI efforts. This paper makes a first step towards guiding the embedding of RRI within higher education. It does so by bringing together academic knowledge with phronesis or practical knowledge about what should be done in an ethical, political, and practical sense. It draws on a literature review and on the reflective practices of partners in the European Commission funded project EnRRICH (Enhancing Responsible Research and Innovation through Curricula in Higher Education), as well as on interviews and case studies gathered as part of the project. The paper suggests elements, especially design principles and a competence framework, for (re)designing curricula and pedagogies to equip higher education students to be and to become responsible actors, researchers, and innovators in a complex world, and to address grand sustainability challenges. In addition, this paper proposes that contemporary higher education teaching and learning policies and strategies, especially those promoting neoliberal agendas and marketized practices, need to adopt a more responsible and responsive ethos to foster the renewal of higher education in times of systemic dysfunction.