<p>Selective solar-driven aerobic oxidation of biomass derivatives into valuable chemicals under ambient conditions is pivotal for sustainable chemical manufacturing but faces challenges from the conflict between O₂ activation kinetics under ambient conditions and selective C–H bond cleavage. This work demonstrates a spatial decoupling strategy in a precisely-engineered 2D/2D g-C₃N₄/ZnIn₂S₄ architecture, where ZnIn₂S₄ domains selectively activate O₂, while adjacent g-C₃N₄ modulates electron transfer to O₂ and tailors 5-hydroxymethylfurfural (HMF) binding configuration for selective C–H bond cleavage. This enables the efficient selective conversion of biomass-derived HMF into 2,5-diformylfuran (DFF) via ambient aerobic photooxidation. When used alone, ZnIn₂S₄ produces mixed reactive oxygen species (·O₂⁻/·OH) due to uncontrolled electron transfer during O₂ activation. <i>In-situ</i> spectroscopy, Kelvin probe force microscopy (KPFM) and density functional theory (DFT) calculations demonstrate, the 2D/2D g-C₃N₄/ZnIn₂S₄, driven by its directed electric field, selectively activates O₂ into ·O₂⁻ at ZnIn₂S₄ domains while suppressing ·OH generation by moderate electron transfer, mitigating over-oxidation. Adjacent g-C₃N₄ domains precisely anchor HMF via −OH group interactions, further steering selective DFF formation. This spatial decoupling achieves a remarkable HMF-to-DFF photo-conversion rate of 1517.5 µmol g⁻¹ h⁻¹ with 99.4% selectivity under ambient air, outperforming many reported state-of-the-art catalysts and maintaining durable cycling performance. Our work establishes a spatial decoupling principle to overcome O₂ activation kinetics and site competition thermodynamics, paving the way for advanced catalyst design for sustainable energy and the environment.</p>