Abstract In plants, large numbers of R genes, which segregate as loci with alternative alleles conferring different levels of disease resistance to pathogens, have been maintained over a long period of evolution. The reason why hosts harbor susceptible alleles in view of their null contribution to resistance is unclear. In rice, a single copy gene, Pi-ta, segregates for 2 expressed clades of alleles, 1 resistant and the other susceptible. We simulated loss-of-function of the Pi-ta susceptible allele using the CRISPR/Cas9 system to detect subsequent fitness changes and obtained insights into fitness effects related to the retention of the Pi-ta susceptible allele. Our creation of an artificial knockout of the Pi-ta susceptible allele suffered fitness-related trait declines of up to 49% in terms of filled grain yield upon the loss of Pi-ta function. The Pi-ta susceptible alleles might serve as an off-switch to downstream immune signaling, thus contributing to the fine-tuning of plant defense responses. The results demonstrated that the susceptible Pi-ta alleles should have evolved pleiotropic functions, facilitating their retention in populations. As Pi-ta is a single copy gene with no paralogs in the genome, its function cannot be compensated by an alternative gene; whereas most other R genes form gene clusters by tandem duplications, and the function could be compensated by paralogs with high sequence similarity. This attempt to evaluate the fitness effects of the R gene in crops indicates that not all disease resistance genes incur fitness costs, which also provides a plausible explanation for how host genomes can tolerate the possible genetic load associated with a vast repertoire of R genes.