Two major diseases that affect grapevine leaves and berries are controlled by the oomycetePythium oligandrum. As the efficacy of biocontrol agents strongly depends on factors such as the trophic behaviors of pathogens and cultivar susceptibility, a two-disease approach was implemented to evaluate the activity ofP. oligandrumagainstBotrytis cinerea(the necrotrophic fungus of gray mold) andPlasmopara viticola(the biotrophic oomycete of downy mildew) on two grapevine cultivars with different susceptibilities to these two pathogens. The results show that grapevine root inoculation withP. oligandrumsignificantly reducedP. viticolaandB. cinereainfection on the leaves of the two cultivars, but with differences. This was observed when the relative expression of 10 genes was measured in response to each pathogen, and could be attributed to their lifestyles, i.e., biotrophic or necrotrophic, which are related to the activation of specific metabolic pathways of the plant. In response toP. viticolainfection, genes from the jasmonate and ethylene pathways were mainly induced, whereas forB. cinerea, the genes induced were those of the ethylene–jasmonate pathway. The different levels of defense againstB. cinereaandP. viticolacould also explain the difference in cultivar susceptibility to these pathogens.