Purpose: This paper aims to explain the relevance of science-society interfaces and their potential for higher education institutions to engage stakeholders in supporting sustainable change in cities, via the transdisciplinary learning and teaching approach of the Regional Centre of Expertise on Education for Sustainable Development Vienna. Design/Methodology/Approach: This case study stresses new forms of transdisciplinary learning and teaching as essential drivers of a sustainable urban development. The inter- and transdisciplinary teaching course "Sustainability Challenge", which has been offered since 2010 as a collaborative project by the four largest universities of Vienna, highlights the value of experienced-based learning approaches and the method of service learning. Special attention is devoted to the opportunities and challenges of the setting provided by the applied science-society interface and the particular method of service learning with its concrete benefits for the city of Vienna. Findings: In analyzing the conceptual framework of the teaching course as well as conducted service learning projects, the authors prove potential benefits of transdisciplinary learning and teaching for real answers to urban sustainability challenges. Portraits of the most successful service learning projects are presented, with partners such as the City of Vienna, an organization and one enterprise. Lessons learned from the case study and key elements of the institutionalized umbrella function of science-society interfaces that provide prerequisites for applying transdisciplinary learning and teaching are shown. Originality/Value: Finally, main requirements, challenges and necessary institutional settings for transdisciplinary learning and teaching are summarized.