Fruit softening, an irreversible ripening process that causes postharvest losses, is mainly attributed to cell wall disassembly, rendering cell-wall-modifying genes critical targets for genetic improvement. However, the molecular mechanism by which expansins loosen the cell wall via the nonenzymatic mechanism, thereby affecting fruit softening, remains largely unknown. In this study, HSM (melting peach, MF) fruits exhibited a rapid decline in firmness, accompanied by more extensive cell wall disassembly and larger intercellular spaces compared with CN14 (non-melting peach, NMF) during the fruit development process. The expression of PpEXPA13, an expansin gene, was significantly higher in HSM than in CN14 during fruit softening. Virus-induced gene silencing in peach delayed firmness loss, while the overexpression of PpEXPA13 in tomato accelerated it. PpEXPA13-OE fruits displayed enlarged intercellular spaces and upregulated expression of multiple cell-wall-modifying genes. Furthermore, a yeast one-hybrid assay identified the transcription factor PpMYC2 as an upstream regulator of PpEXPA13. PpMYC2 specifically binds to the MYC box (CACGTG) in the PpEXPA13 promoter. These findings reveal that PpMYC2 activates PpEXPA13 expression, which might lead to cell wall disassembly and promote peach fruit softening.