The progression of myocardial ischemia-reperfusion injury (MIRI) is orchestrated by a decisive, bidirectional dialogue between mitochondrial reactive oxygen species (mtROS) and mitophagy. This review advances the concept of a dynamic "mtROS-mitophagy axis" as the central redox hub determining cardiomyocyte fate. We systematically dissect how moderate mtROS initiates protective mitophagy via key pathways (e.g., PINK1/Parkin, FUNDC1) and reinforces endogenous defenses through the Sirt3-FoxO3a integrator. Conversely, an mtROS burst disrupts this axis, triggering a vicious cycle of oxidative damage, impaired autophagic flux, and Drp1-mediated pathological fission. Critically, we emphasize the double-edged and temporally governed nature of this axis, arguing that its precise spatiotemporal modulation represents the next frontier in cardioprotection. Beyond mechanism, this synthesis provides a unified framework for developing novel therapies and for evaluating the cardiac safety of pharmacological agents, directly aligning with the core pursuits of cardiovascular redox biology and toxicology.