Economic ups and downs condition science and innovation. The research strength of business firms and their cooperation with universities are important functions of science systems. The aim of this research is to analyse some of the links between business scientific output co-creation and impact throughout the economic cycle. Economic growth increases the probability of firms increasing both their scientific knowledge co-creation output and their scientific impact (during crises), until reaching an inflection point, after which those relationships become negative (during expansions). Co-creation with universities intensifies the scientific impact of firms’ output; however, although in theory this effect should vary according to the economic phase, the evidence shows that it remains steady. In this study, the theory is grounded through interviews with key university and firm coauthors, and an empirical test is conducted on publications from 15,000 Spanish firms between 2000 and 2016 and their citations—a period which includes the Spanish Great Recession (2008–2014). The analysis suggests that policies to promote business cocreation output with universities should be more stable throughout economic cycle: in expansions, governments should maintain the support for co-creation that is typical of crises; in crises, governments should not expect co-creation with universities to have an even greater positive effect on firms’ scientific quality than it already has during expansions.