Benzothiadiazole (BTH) and chitosan (CHT) belong to a class of agrochemicals activating the plant defense mechanisms against various pathogens. In this work, their efficacy against downy mildew, one of the most widespread and destructive diseases of the grapevine in the world, was evaluated. Open-field treatments were carried out in a vineyard of Groppello, a native cultivar of northern Italy, for two consecutive phytoiatric campaigns. In both years, BTH and CHT proved to be active, resulting in significantly lower percentages of disease incidence and disease severity than those recorded in the control plots. In particular, the CHT-copper combination was able to decrease the infection symptoms with values ranging from 60% to over 90% depending on the environmental conditions and the disease pressure. Our results suggested that plant defense inducers could be successfully used in crop protection as part of integrated pest management due to their effectiveness, as well as reduced environmental impact and low fitness costs for the plant.