Pathogenic bacteria taken up into the macrophage phagosome are the target of many anti-microbial mechanisms. Although mitochondria-derived antimicrobial effectors like reactive oxygen species (mROS) aid in bacterial killing, it is unclear how these effectors reach bacteria within the phagosomal lumen. We show here that endoplasmic reticulum stress triggered upon methicillin-resistant Staphylococcus aureus (MRSA) infection induces mROS that are delivered to bacteria-containing phagosomes via mitochondria-derived vesicles (MDVs). The endoplasmic reticulum stress sensor IRE1α induces mROS, specifically hydrogen peroxide (mHO), upon MRSA infection. MRSA infection also stimulates the generation of MDVs, which require the mitochondrial stress response factor Parkin, and contributes to mHO accumulation in bacteria-containing phagosomes. Accumulation of phagosomal HO requires Toll-like receptor signaling and the mitochondrial enzyme superoxide dismutase-2 (Sod2), which is delivered to phagosomes by MDVs. Sod2 depletion compromises mHO production and bacterial killing. Thus, mitochondrial redox capacity enhances macrophage antimicrobial function by delivering mitochondria-derived effector molecules into bacteria-containing phagosomes.