In discussions about Entrepreneurial Universities, it is essential to recognize that academics are at its heart and almost certainly the most important protagonists, particularly those who engage in academic spin-off creation (ASOs). However, understanding their entrepreneurial behavior is still limited, as is the connection to other important activities, such as University-Business Collaboration (UBC). Literature suggests that ASOs creation is conditioned by a great number of factors, but prior studies are limited in their approach and do not include the effect of the participation in other collaborative activities with the industry. This gap is addressed by unlocking spin-off creation from a multidisciplinary approach, integrating both psychological and sociological antecedents, as well as considering the influence of UBC in a much-needed international context. With data from a sample of 2,188 academics from 33 European countries, eleven hypotheses are tested using a structural equation model – The UBC-ASOs Model. Results show the relevance of the three UBC dimensions considered (attitude towards UBC, cultural support for UBC and UBC self-efficacy) for ASOS creation, as well as the effect of the cultural aspect in the psychological domain. Motivations are defined as drivers of UBC, while academics’ social capital enhances their cultural support for UBC but does not influence their attitude towards UBC or their UBC self-efficacy. The central role of UBC reveals the importance of re-thinking academic entrepreneurship research from the broader perspective of collaboration, while having valuable policy and managerial implications and providing key insights on how to develop Entrepreneurial Universities.