In the last decade, an extraordinary policy effort has been put in place to reduce the use of chemical plant protection products (PPPs) in French agriculture. This was done through a National Action Plan called Ecophyto which is the French response to the EU Framework Directive on the sustainable use of PPPs. The change in crop protection, required to meet the ambitious goal of Ecophyto, has generated three major research needs: first, exploration of new fields of knowledge (e.g., links between cropping systems, biodiversity and pest regulation), second, support of the unprecedented devices (e.g., pest monitoring system and farm network) put in place to accompany the transition phase, and third, reconsideration of issues related to pest management methods in the context of the changes of farming practices promoted by Ecophyto. To address these new research needs, Ecophyto has devoted a specific research and innovation (R&I) axis which prioritized relevant research questions covering eight thematic areas: (i) pest monitoring and decision-making, (ii) design of IPM solutions, (iii) diversification of pest control methods, (iv) durability and sustainability of these methods, (v) socio-economic aspects of the transition toward a low-input crop protection system, (vi) contribution of public policy for such a transition, (vii) development of indicators to assess the use and impacts of chemical PPPs, and (viii) effects on human health due to exposure to chemical PPPs. The resulting scientific program was disseminated through a diversity of calls for proposals which vastly mobilized public research, in partnership with agricultural experimentation networks and private research. This initiative has translated into dynamic and significant advances made by research which, in part, are already discernible. It will eventually produce a corpus of scientific knowledge and technical innovations which can contribute to the expected transition toward a low-input crop protection system, as long as farmers are associated in the design of sustainable IPM solutions and other concerned stakeholders of the sociotechnical system are mobilized.