The INVEST European University Alliance aims at shaping a more sustainable and responsible future across Europe. Sustainability and responsibility are the guiding principles in all the processes related to the alliance’s research, education, administration, and service to society. The key actions addressing the diverse, multi-professional and transdisciplinary group of researchers, educationalists, and practitioners in the field, aim at building competences and skills for a brighter future in all the partner regions. To make this real, the alliance has established a community of practice to frame, support and foster the systematic and strategic development of competences, skills, and actions. This study reports the research-based establishment process of the INVEST alliance’s Community of Practice (CoP) for sustainability. The paper first valorises the principles of CoP and its theoretical foundations. It then sheds light on the processes of building the key CoP elements: strategic planning process, and capacity building. Finally, it discusses, how the INVEST CoP aims to foster sustainability and responsibility holistically to promote more sustainable regional development throughout the alliance partner countries. This paper aims to enrich the conceptual discussion and long-term capacity-building process addressing sustainability and responsibility across European higher education and its regional stakeholders. This research also supports the European Union’s goal of increasing CoPs by giving valuable insight into CoPs in the context of higher education and European University Alliances.