Wounding is a trigger for both regeneration and defense in plants, but it is not clear whether the two responses are linked by common activation or regulated as trade-offs. Although plant glutamate-receptor-like proteins (GLRs) are known to mediate defense responses, here, we implicate GLRs in regeneration through dynamic changes in chromatin and transcription in reprogramming cells near wound sites. We show that genetic and pharmacological inhibition of GLR activity increases regeneration efficiency in multiple organ repair systems in Arabidopsis and maize. We show that the GLRs work through salicylic acid (SA) signaling in their effects on regeneration, and mutants in the SA receptor NPR1 are hyper-regenerative and partially resistant to GLR perturbation. These findings reveal a conserved mechanism that regulates a trade-off between defense and regeneration, and they also offer a strategy to improve regeneration in agriculture and conservation.