Pathogen effectors can suppress various plant immune responses, suggesting their multiple targets in the host. To understand the mechanisms underlying plasma membrane-associated and effector-mediated immunity, we performed Phytophthora capsici CRISIS screening. In Nicotiana benthamiana, cell death induced by the RxLR effector CRISIS2 is inhibited by irreversible plasma membrane H+-ATPase (PMA) activator fusicoccin. Biochemical and gene silencing analyses revealed that CRISIS2 physically and functionally associates with PMAs and induces cell death independent of immune receptors. CRISIS2 induces apoplastic alkalization by suppressing PMA activity by association with the C-terminal regulatory domain of PMA. In planta expression of CRISIS2 significantly enhanced virulence of P. capsici, whereas host-induced gene silencing of CRISIS2 compromised disease symptom and biomass of P. capsici. Furthermore, co-immunoprecipitation assays revealed CRISIS2 associates with BAK1, the co-receptor of PRRs. CRISIS2 interferes with the FLS2-BAK1 complex induced by flagellin perception and impairs downstream signaling from PRR complex. Proteomics and gene silencing assays identified putative PRRs negatively regulate the virulence of P. capsici in N. benthamiana as interactors of CRISIS2 and BAK1. Our study identified a novel RxLR effector playing multiple roles in suppression of plant defense and induction of cell death to support the pathogen hemibiotrophic life cycle in the host plant.