Nanocrystalline ceramics offer interesting and useful physical properties attributed to their inherent large volume fraction of grain boundaries. At the same time, these materials are highly unstable, being subjected to severe coarsening when exposed at moderate to high temperatures, limiting operating temperatures and disabling processing conditions. In this work, we designed highly stable nanocrystalline yttria stabilized zirconia (YSZ) by targeting a decrease of average grain boundary (GB) energy, affecting both driving force for growth and mobility of the boundaries. The design was based on fundamental equations governing thermodynamics of nanocrystals, and enabled the selection of lanthanum as an effective dopant which segregates to grain boundaries and lowers the average energy of YSZ boundaries to half. While this would be already responsible for significant coarsening reduction, we further experimentally demonstrate that the GB energy decreases continuously during grain growth caused by the enrichment of boundaries with dopant, enhancing further the stability of the boundaries. The designed composition showed impressive resistance to grain growth at 1100 °C as compared to the undoped YSZ and opens the perspective for similar design in other ceramics.