This paper contributes to expand our understanding of academics’ participation in academic entrepreneurship and technology transfer by exploring two specific knowledge-based antecedents which emanates from research activities: upstream knowledge sources gained through outstanding individuals’ contributions to scientific discoveries and downstream knowledge sources obtained through researchers’ interactions with potential beneficiaries of research. We find a reinforcing effect for those scientists who jointly combine both knowledge sources: they are more likely to be involved in academic spin-offs. This reinforcing effect is not observed, however, for the involvement in technology transfer. Additionally, we examine the influence exerted by a supportive organisational environment for commercialisation activities at the department or research institute levels. Our results show that organisational support is particularly positive and significant in the case of scientists who exhibit lower levels of upstream knowledge sources (that is, those scientists with comparatively weaker profiles in terms of outstanding scientific contributions over their professional trajectories).