Insights into the catalytic transformation of propane to propene on V‐apatites catalysts are provided based on structure‐reactivity relationships. Substitution of phosphates by vanadates in the hydroxyapatite structure leads to the formation of Ca10(PO4)6‐x(VO4)x(OH)2‐yOy V‐oxy‐hydroxy‐apatite solid solutions (x = 0→ 6). Bulk vanadium incorporation promotes (i) calcium rich terminations (XPS, CO adsorption), (ii) proton deficiency inside the OH‐ channels (1H NMR) giving rise to O2‐ native species, (iii) the thermally‐activated formation of additional O2‐ species along the OH‐ channels resulting in H‐bonding interaction (in situ DRIFT) and (iv) the proton conduction process that eventually results in the surface exposure of O2‐ species (in situ impedance spectroscopy). The exposure of Ca2+‐O2‐ surface acid‐base pairs allows the dissociation of hydrogen, emphasizing the strong basicity of the related O2‐ species. Whereas an increasing vanadium content is beneficial to propene selectivity, it scarcely impacts propane conversion. The reaction proceeds mainly upon oxidative dehydrogenation, even if the minor dehydrogenation route is also observed. Surface O2‐ generated thanks to proton mobility are involved in the C‐H bond activation, as shown by the synergistic effect between the oxidative dehydrogenation of propane reaction and the bulk proton conduction measured under operando conditions. This puts emphasis on the key role of strong basic sites for propane activation.