Plant genomes encode large numbers of nucleotide-binding, leucine-rich repeat (NB-LRR) proteins, many of which are active in pathogen detection and defense response induction. NB-LRR proteins fall into two broad classes: those with a Toll and interleukin-1 receptor (TIR) domain at their N-terminus and those with a coiled-coil (CC) domain at the N-terminus. Within CC-NB-LRR-encoding genes, one basal clade is distinguished by having CC domains resembling the Arabidopsis thaliana RPW8 protein, which we refer to as CCR domains. Here, we show that CCR-NB-LRR-encoding genes are present in the genomes of all higher plants surveyed, and that they comprise two distinct subgroups: one typified by the Nicotiana benthamiana N-required gene 1 (NRG1) protein and the other typified by the Arabidopsis activated disease resistance gene 1 (ADR1) protein. We further report that, in contrast to CC-NB-LRR proteins, the CCR domains of both NRG1- and ADR1-like proteins are sufficient for the induction of defense responses, and that this activity appears to be SGT1-independent. Additionally, we report the apparent absence of both NRG1 homologs and TIR-NB-LRR-encoding genes from the dicot Aquilegia coerulea and the dicotyledonous order Lamiales as well as from monocotyledonous species. This strong correlation in occurrence is suggestive of a functional relationship between these two classes of NB-LRR proteins.