Hydrogen pickup poses a challenging safety limit for employing zirconium alloys in nuclear reactors. Previous experimental observations guided the empirical design of new alloys but the mechanisms of hydrogen pickup remained undecipherable. Here, we assess two critical prongs of hydrogen pickup through the ZrO2 passive film that serves as a surface barrier; the solubility of hydrogen in it – a detrimental process, and the ease of H2 gas evolution from its surface – a desirable process. By combining statistical thermodynamics and density functional theory calculations, we show that hydrogen solubility in ZrO2 exhibits a valley-shape as a function of the chemical potential of electrons, µe, that is tunable in ZrO2 by doping. For designing zirconium alloys resistant against hydrogen pickup, we target either a dopant that thermodynamically minimizes the solubility of hydrogen in ZrO2 at the bottom of this valley (such as Cr), or a dopant that maximizes µe and kinetically accelerates proton reduction and H2 evolution at the surface of ZrO2 (such as Nb, Ta, Mo, W, or P).