This paper provides novel evidence on co-evolution patterns of the technological specialization of innovation activities of firms and academic institutions located in the same European region during the years from 2003 to 2014. We exploit a novel and unique dataset merging data on EU-funded R&D projects, universities, patents, and economic region-level data for a large sample of universities and firms co-located in geographical areas at the third level of the Nomenclature of Territorial Units for Statistics (NUTS3), which correspond to a sub-regional scale of analysis. Our results indicate the presence of substantial heterogeneity across the analyzed EU regions with respect to the co-evolution of industry and academia specializations. In particular, we find that the specialization into a new technological domain is led by the local academic research system only in a few cases. We also document that a number of factors, at both the university and region levels, are associated with convergent or divergent processes in the relative specialization of the innovation activities carried out by firms and universities co-located in the same region.