Dilemma of dielectric breakdown has perplexed researchers for decades while intrinsic factors accounting for dielectric breakdown strength (DBS) is still unsettled. In this work to address the great deterioration of DBS after LiF acceptor doping in MgO (LMO), high throughout first principles calculation is carried out to screen nearly 30 cations from donor doping perspective. The work function from the theoretical calculation, as a descriptor correlated to electronic property, displays a linear correlation with experimental DBS while Mn is proven to be the best candidate dopant for its greatly improvement on work function of LMO system and therefore a markedly enhanced DBS. Detailed analysis manifests that MnCO3 incorporation further decreases the sintering temperature of LMO to 900 °C and also leads to defect associations between oxygen vacancies and cation substitutional defects, causing distinct change in dielectric behavior and conduction mechanism. Afterwards, beneficial effects of grain refinement and increased grain boundary resistivity on DBS are analyzed using phase field modeling method. With all these merits, nearly 85% improvement in DBS is achieved in 1 wt% MnCO3 tailored LMO. This work not only reveals the decisive role of work function in DBS prediction therefore shed light on composition design of dielectrics, but also provides a paradigm combining ions screening, theoretical prediction, experiments and simulation together to greatly accelerate the materials research.