Plasmopara viticola, the causal agent of grapevine downy mildew, is one of the most important pathogens affecting vineyards worldwide. In Italy, the 2023 growing season was among the most critical in recent years, with severe downy mildew outbreaks favored by exceptionally conducive climatic conditions. Proper management minimizes yield losses and reduces reliance on synthetic and copper-based fungicides, thereby mitigating risks for the environment and consumer health. Our research aimed to develop an effective and sustainable biological control strategy based on the application of a beneficial microorganism combined with natural compounds, while reducing copper inputs. Over two years, different biological and integrated control strategies were compared with conventional programs based on synthetic anti-downy mildew fungicides. Overall, the results highlighted the importance of: (i) a preventive approach, involving early-season applications targeting primary inoculum and initial infections; and (ii) an integrated strategy, combining different anti-downy mildew formulations with multiple modes of action. Across two years of field trials, the greatest reduction in disease incidence was achieved with integrated control strategies in which the bioformulate YSY^®, based on the beneficial yeast PT22AV, was applied early in the season, in combination with other commercial formulations based on copper and plant extracts.