In Arabidopsis (Arabidopsis thaliana), MICRORCHIDIA 1 (MORC1), a member of the MORC family of evolutionarily conserved GHKL-type ATPases, plays important roles in multiple layers of plant immunity. However, the molecular mechanism by which MORC1 regulates plant immunity remains obscure. Here, we report that the pathogen-responsive kinase CALCIUM-DEPENDENT PROTEIN KINASE 5 (CPK5) directly interacts with and phosphorylates MORC1, thereby promoting its stability and nuclear translocation. In the nucleus, MORC1 associates with the NONEXPRESSOR OF PATHOGENESIS-RELATED GENES 1 (NPR1)-TGACG-BINDING FACTOR (TGA) transcriptional complex to upregulate defense-responsive genes and promote plant resistance against several pathogens, such as the bacterial pathogen Pseudomonas syringae pv. tomato DC3000 and fungal pathogen Botrytis cinerea. Therefore, this study uncovers a MORC1-mediated immune signaling pathway, in which the CPK5-MORC1-NPR1-TGA module transduces Ca2+ signals, leading to the upregulation of defense genes involved in plant immunity.