High-entropy oxides (HEOs) containing multiple 3d cations have recently attracted attention as bifunctional oxygen electrocatalysts, but the controlled introduction of oxygen vacancies and their impact on zinc–air battery (ZAB) performance remain insufficiently explored [1-3]. Here, we report a simple yet effective strategy to engineer oxygen vacancies in spinel (FeCrCoMnZn)₃O₄₋δ high-entropy oxides by altering the calcination atmosphere from air to vacuum and systematically correlating the resulting defect chemistry with oxygen evolution (OER) and oxygen reduction (ORR) activity as well as full-cell ZAB performance. Co-precipitated precursors were calcined at 900 °C in air (HEO-Air) or vacuum (HEO-Vac), yielding single-phase spinel powders confirmed by X-ray diffraction and Rietveld refinement. Transmission electron microscopy, SAED, and HAADF-STEM/EDS mapping verify homogeneous multi-cation distribution and a stable spinel lattice in both samples, including after extended electrochemical cycling. X-ray photoelectron spectroscopy reveals a markedly higher oxygen-vacancy fraction in HEO-Vac than in HEO-Air, which is further supported by a stronger EPR signal, evidencing enhanced vacancy concentration under vacuum calcination. In alkaline electrolyte, HEO-Vac exhibits superior OER activity with a reduced overpotential, lower Tafel slope, and significantly smaller charge-transfer resistance compared to HEO-Air. For ORR, HEO-Vac delivers a more positive potential at −1 mA cm⁻² and a higher electron transfer number (n ≈ 3.6) than HEO-Air (n ≈ 1.5), consistent with a predominantly four-electron pathway and improved bifunctionality, reflected in a lower bifunctional index of 0.89 V. When integrated as the air cathode catalyst in aqueous ZABs, HEO-Vac enables a smaller charge–discharge voltage gap and a much larger specific capacity (576 mAh gZn⁻¹ at 5 mA cm⁻²), corresponding to ~70% of the theoretical Zn capacity. The HEO-Vac–based ZAB also demonstrates outstanding rate capability, high specific energy (~662 Wh kg⁻¹), Coulombic efficiencies up to 96%, and stable cycling over 300 h with minimal degradation. Overall, this study shows that tuning the synthesis atmosphere is a powerful, scalable lever to modulate oxygen vacancy content and charge-transfer characteristics in high-entropy spinel oxides, thereby enabling durable, high-performance bifunctional catalysts for next-generation rechargeable zinc–air batteries.