SUMMARYDuring inflammation, the skin deploys antimicrobial peptides (AMPs) yet during allergic inflammation it becomes more susceptible toStaphylococcus aureus. To understand this contradiction, single-cell sequencing ofIl4ra−/−mice combined with skin microbiome analysis reveals that lower production of AMPs from interleukin-4 receptor α (IL-4Rα) activation selectively inhibits survival of antibiotic-producing strains of coagulase-negativeStaphylococcus(CoNS). Diminished AMPs under conditions of T helper type 2 (Th2) inflammation enable expansion of CoNS strains without antibiotic activity and increaseStaphylococcus aureus(S. aureus), recapitulating the microbiome on humans with atopic dermatitis. This response is rescued inCamp−/−mice or after topical steroids, since further inhibition of AMPs enables survival of antibiotic-producing CoNS strains. In conditions of Th17 inflammation, a higher expression of host AMPs is sufficient to directly inhibitS. aureussurvival. These results show that antimicrobials produced by the host and commensal bacteria each act to controlS. aureuson the skin.