Phytosulfokine (PSK) is a plant growth-promoting peptide hormone that is perceived by its cell surface receptors PSKR1 and PSKR2 in Arabidopsis. Plants lacking the PSK receptors show phenotypes consistent with PSK signaling repressing some plant defenses. However, the degree to which such repression is an indirect effect of receptor mutations or directly linked to the presence and effects of PSK was unclear.To fill this gap in knowledge, comprehensive transcriptional profiling of Arabidopsis treated with PSK was performed and PSK treatment’s effects on plant defense readouts were monitored. WRKY transcription factors emerged as key regulators of PSK-responsive genes, sharing commonality with pathogen-associated molecular pattern (PAMP) responses, but exhibiting opposite regulatory directions. These PSK-induced transcriptional changes were accompanied by biochemical and physiological changes that reduced PAMP responses, notably Mitogen-Activated Protein Kinase phosphorylation (previously implicated in WRKY activation) and the cell wall modification of callose deposition. My study indicates stronger suppression of defense genes than induction of growth-related genes and supports a role for PSK signaling in mediating a trade-off between plant growth and defense.