The effect of electron quantum confinement on the surface reactivity of ultrathin metal films is explored by comparing the initial oxidation rate of atomically flat magnesium films of different thickness, using complementary microscopy techniques. Pronounced thickness-dependent variations in the oxidation rate are observed for well ordered films of up to 15 atomic layers. Quantitative comparison reveals direct correlation between the surface reactivity and the periodic changes in the density of electronic states induced by quantum-well states crossing the Fermi level.