Grapevine downy mildew, caused by the oomycete Plasmopara viticola, is one of the most considerable production challenges for the grape and wine industries. P. viticola injects a plethora of effectors into host cells to disrupt immune processes, but the mechanisms by which these effectors act at the molecular level have not been well characterized. Herein, we show that a candidate P. viticola Avirulence Homolog (Avh) RxLR effector gene, designated PvAvh77, was strongly up-regulated during the initial stages of P. viticola infection in Vitis vinifera. Further experiments demonstrated that PvAvh77 could trigger nonspecific cell death when expressed in the wild grapevine Vitis riparia and in tobacco (Nicotiana benthamiana and Nicotiana tabacum). We also found that a truncated form of PvAvh77, designated PvAvh77-M2, was more active in inducing cell death in N. benthamiana and V. riparia than full-length PvAvh77. Furthermore, PvAvh77-induced cell death required BAK1/SOBIR1, NDR1, SGT1, HSP90, and RAR1, but not EDS1 or MAPK pathway-related genes. Ectopic expression of PvAvh77 in Vitis vinifera cv. Thompson Seedless leaves neutralized host immunity and enhanced colonization by P. viticola, and the immune-inhibiting activity of PvAvh77 on susceptible Eurasian grapevine depended on its nuclear localization. Agrobacterium-mediated transient expression of PvAvh77 in N. benthamiana leaves also interfered with the immune response triggered by flg22. Using a yeast signal sequence trap approach, we showed that the signal peptide of PvAvh77 is functional in yeast. Moreover, PvAvh77 with a signal peptide stimulated plant immunity responses in the apoplast. Notably, application of exogenous purified PvAvh77-M2 effectively initiated defense responses in grapevines, as evidenced by increased accumulation of salicylic acid (SA) and H2O2, and reduced infection of inoculated P. viticola. In summary, we identified a novel effector, PvAvh77, from P. viticola, which has the potential to serve as a plant immunity inducer.