The microrchidia (MORC) proteins, a subset of the GHKL ATPase superfamily, were recently described as components involved in transcriptional gene silencing and plant immunity in Arabidopsis. To assess the role of MORC1 during resistance to Phytophthora infestans in solanaceous species, we altered the expression of the corresponding MORC1 homologs in potato, tomato, and Nicotiana benthamiana. Basal resistance to P. infestans was compromised in StMORC1-silenced potato and enhanced in overexpressing lines, indicating that StMORC1 positively affects immunity. By contrast, silencing SlMORC1 expression in tomato or NbMORC1 expression in N. benthamiana enhanced basal resistance to this oomycete pathogen. In addition, silencing SlMORC1 further enhanced resistance conferred by two resistance genes in tomato. Transient expression of StMORC1 in N. benthamiana accelerated cell death induced by infestin1 (INF1), whereas SlMORC1 or NbMORC1 suppressed it. Domain-swapping and mutational analyses indicated that the C-terminal region dictates the species-specific effects of the solanaceous MORC1 proteins on INF1-induced cell death. This C-terminal region also was required for homodimerization and phosphorylation of recombinant StMORC1 and SlMORC1, and its transient expression induced spontaneous cell death in N. benthamiana. Thus, this C-terminal region likely plays important roles in both determining and modulating the biological activity of MORC1 proteins.