Disease severity in atopic dermatitis is associated with Staphylococcus aureus skin colonization; however, how dysbiosis of the skin microbiome may influence atopic dermatitis pathophysiology is unknown. Williams et al. show that proteases and phenol-soluble modulin-α (PSMα) secreted by S. aureus cause epidermal proteolysis and skin barrier damage in mice, thus promoting inflammation. Coagulase-negative staphylococci (CoNS) that are found on human skin were shown to secrete autoinducing peptides that inhibit accessory gene regulator quorum sensing in S. aureus, thus reducing PSMα expression. These autoinducers also reduced S. aureus-induced dermatitis in mice. Skin microbiome analyses of individuals with atopic dermatitis suggested that the ratio of CoNS to S. aureus has a role in atopic dermatitis pathogenesis.