Methicillin-resistant <i>Staphylococcus aureus</i> (MRSA) infections are still difficult to treat, despite the availability of many FDA-approved antibiotics. Thus, new compound scaffolds are still needed to treat MRSA. The oxadiazole-containing compound, <b>HSGN-94</b>, has been shown to reduce lipoteichoic acid (LTA) in <i>S. aureus</i>, but the mechanism that accounts for LTA biosynthesis inhibition remains uncharacterized. Herein, we report the elucidation of the mechanism by which <b>HSGN-94</b> inhibits LTA biosynthesis via utilization of global proteomics, activity-based protein profiling, and lipid analysis via multiple reaction monitoring (MRM). Our data suggest that <b>HSGN-94</b> inhibits LTA biosynthesis via direct binding to PgcA and downregulation of PgsA. We further show that <b>HSGN-94</b> reduces the MRSA load in skin infection (mouse) and decreases pro-inflammatory cytokines in MRSA-infected wounds. Collectively, <b>HSGN-94</b> merits further consideration as a potential drug for staphylococcal infections.