Staphylococcus aureusis the leading cause of skin and soft tissue infections and is a major health burden due to the emergence of antibiotic-resistant strains. To address the unmet need of alternative treatments to antibiotics, a better understanding of the protective immune mechanisms againstS. aureusskin infection is warranted. Here, we report that tumor necrosis factor (TNF) promoted protection againstS. aureusin the skin, which was mediated by bone marrow–derived immune cells. Furthermore, neutrophil-intrinsic TNF receptor (TNFR) signaling directed immunity againstS. aureusskin infections. Mechanistically, TNFR1 promoted neutrophil recruitment to the skin, whereas TNFR2 prevented systemic bacterial dissemination and directed neutrophil antimicrobial functions. Treatment with a TNFR2 agonist showed therapeutic efficacy againstS. aureusandPseudomonas aeruginosaskin infections, which involved increased neutrophil extracellular trap formation. Our findings revealed nonredundant roles for TNFR1 and TNFR2 in neutrophils for immunity againstS. aureusand can be therapeutically targeted for protection against bacterial skin infections.