Eccentric contraction- (ECC) induced force loss is a hallmark of dystrophin-deficient (mdx) skeletal muscle that is used to assess efficacy of potential therapies for Duchenne muscular dystrophy. While virtually all key proteins involved in muscle contraction have been implicated in ECC force loss, a unifying mechanism that orchestrates force loss across such diverse molecular targets has not been identified. We show that bypassing defective hydrogen sulfide metabolism in mdx muscle with NaHS prevents ECC force loss. We also show that the cysteine proteome of skeletal muscle functions as a redox buffer in WT and mdx muscle during ECCs, but that buffer capacity in mdx muscle is significantly compromised by elevated basal protein oxidation. Finally, chemo-proteomic data suggest that hydrogen sulfide protects several proteins central to muscle contraction against irreversible oxidation through persulfidation-based priming. Our results support a unifying, redox-based mechanism of ECC force loss in mdx muscle.