Cation diffusion controls mass transport and microstructural evolution in zirconia above 1200 oC. In past research, its experimentally measured activation energy of 5 eV cannot be reproduced by computer simulation, which gives >10 eV and a cation vacancy mechanism implicating enhanced diffusion in oxidizing atmosphere, contradicting experimental evidence. This thesis was undertaken to answer these questions and to explore new ground in cation kinetics. To help search for low-energy configurations in zirconia alloys, we employed crystal chemistry to boost sampling efficiency, by >1,000 times, and obtained plausible “ground states” to launch ab-initio calculations for cation defects and migration. The combined formation and migration energy, about 5 eV, is in agreement with experimental observations. Our calculations further found an extra electron can facilitate migration of a reduced cation, because electron localization at the saddle point can significantly lower the energy. Confirming recent reports, we found graded grain size under large electrical loading, implicating a 10^4× enhancement in cation kinetics in favor of the cathode side; similarly enhanced kinetics was observed under reducing conditions. This connection allowed us to map local oxygen potential using grain growth kinetics, thus obtaining a direct measure of electrode polarization in zirconia for the first time. In addition to the well-known effects of electrode kinetics, a new effect caused by the association of electrons/holes and lattice oxygens/defects was revealed by cavitation due to vacancy condensation. Such association led to predictions on oxygen potential distributions that agree with experimentally observed grain size distributions. Lastly, we discovered a sharp mobility transition in zirconia grain growth at around 1200 oC, caused by crossover from boundary-mobility control to junction-mobility control. A theory was formulated to predict new growth exponents and grain size variations. When mobility inhomogeneity was further considered, we obtained predictions in agreement with the measured statistics and kinetics at low temperatures. By placing several fundamental aspects of cation diffusion in zirconia on a firmer footing, this thesis will help understanding and design of zirconia ceramics. Such understanding may be used to improve zirconia fabrication and applications at high temperatures, especially under a large electrical or chemical driving force.