Academic spin-offs (ASOs) are companies with a strong international vocation for two main reasons: first, they market their products and services in global market niches to profit from their high investment in R&D, characteristic of the sectors in which ASOs operate; and second, as a consequence of the international training and experience and of the international networks that the founding academic entrepreneurs of these companies tend to enjoy, derived from their scientific activity. Despite this natural tendency to internationalize, ASOs and specifically the founding academic entrepreneurs of these companies present certain difficulties in accessing resources for internationalization and in achieving credibility in foreign markets due to their university origins. Based on the resource-based view (RBV), and network theory (NT), this work proposes that the human capital, the social capital, and the psychological capital of the academic entrepreneur could compensate for these obstacles, providing key resources for the internationalization of their companies. The results contribute to the RBV, NT, and academic entrepreneurship and internationalization literature since they show that human capital, in terms of the international experience and training of the academic entrepreneur, their networks of relationships with international academic agents, and their psychological capital, are all antecedents of the internationalization of ASOs. However, the networks of academic entrepreneur relationships with international market agents appear to be irrelevant in the process of international expansion of ASOs.