This paper examines the association between university–industry collaboration and firm innovation performance, and the effect of informal mechanisms of knowledge transfer on such an association, using data from a survey of 245 firms in Ghana and employing partial least squares structural equation modelling. The results are of significant relevance to the business community and policy-makers in Ghana and West African. We find that while university–industry collaboration is positively related to innovation performance in firms, informal mechanisms of university knowledge transfer do not and negatively moderate the positive association between university–industry collaboration and innovation performance in firms. It is also found that to facilitate innovation outcomes, formal, legal binding contracts are required. The study recommends that university knowledge generation and innovation policies in Ghana encourage formal collaboration between knowledge exchange actors. It is also suggested that improvements need to be made to the efficacy of intellectual property legislation in Ghana.