SUMMARYPlants usually employ resistance (R) genes to defend against the infection of pathogens, and most R genes encode intracellular nucleotide‐binding, leucine‐rich repeat (NLR) proteins. The recognition between R proteins and their cognate pathogens often triggers a rapid localized cell death at the pathogen infection sites, termed the hypersensitive response (HR). Metacaspases (MCs) belong to a cysteine protease family, structurally related to metazoan caspases. MCs play crucial roles in plant immunity. However, the underlying molecular mechanism and the link between MCs and NLR‐mediated HR are not clear. In this study, we systematically investigated the MC gene family in maize and identified 11 ZmMCs belonging to two types. Further functional analysis showed that the type I ZmMC1 and ZmMC2, but not the type II ZmMC9, suppress the HR‐inducing activity of the autoactive NLR protein Rp1‐D21 and of its N‐terminal coiled‐coil (CCD21) signaling domain when transiently expressed in Nicotiana benthamiana. ZmMC1 and ZmMC2 physically associate with CCD21 in vivo. We further showed that ZmMC1 and ZmMC2, but not ZmMC9, are predominantly localized in a punctate distribution in both N. benthamiana and maize (Zea mays) protoplasts. Furthermore, the co‐expression of ZmMC1 and ZmMC2 with Rp1‐D21 and CCD21 causes their re‐distribution from being uniformly distributed in the nucleocytoplasm to a punctate distribution co‐localizing with ZmMC1 and ZmMC2. We reveal a novel role of plant MCs in modulating the NLR‐mediated defense response and derive a model to explain it.