Macrophage activation is essential for innate immunity and antimicrobial defense. We show that Enterococcus faecalis suppresses macrophage activation through lactic-acid-mediated acidification of the extracellular environment, enabling pathogen persistence. E. faecalis-derived lactic acid acts via the lactate transporter monocarboxylate transporter 1 (MCT-1) and the sensor GPR81 to initiate complementary mechanisms that collaboratively reduce nuclear factor κB (NF-κB) activity. Lactic acid acts through MCT-1 to inhibit extracellular signal-regulated kinase and STAT3 phosphorylation, leading to reduced levels of the adaptor MyD88 involved in NF-κB activation. Lactic acid signaling to GPR81 induces phosphorylation of the transcription factor YAP, ultimately attenuating NF-κB signaling. A bacterial mutant lacking lactate dehydrogenase is unable to acidify the environment and thus fails to inhibit NF-κB. In a murine wound infection model, lactic-acid-driven immunosuppression enables prolonged E. faecalis persistence and enhances the fitness of co-infecting bacteria such as Escherichia coli. These findings reveal how bacterial lactic acid subverts innate immunity to support chronic and polymicrobial infections.