While there is a large body of literature on the benefits of open innovation, little is known about the knowledge flows and the interrelationship of the purposeful and serendipitous spillover of knowledge flows that deliver value from international open innovation (IOI) collaborations. This study examines these knowledge flows occurring from IOI and the extent to which the entrepreneurial ecosystem (EE) context, knowledge management (KM) capabilities of the firm, and knowledge spillovers (KS), nurture IOI engagement. A quantitative study is adopted where data on 98,809 firms from 15 European Union countries to empirically tested a proposed model through multiple linear regressions of logit models. The results highlight the positive effect of KS on IOI engagement, and the positive mediating effect of KM capability on the relationship between KS and IOI. Additionally, the results show a positive moderating effect of the EE on the relationship between the firm's KM capability and IOI engagement. Additionally, the findings emphasize the beneficial nature of the EE on nurturing KM capabilities within firms located in the ecosystem and its impact on nurturing KS within the network.