Time-dependent, two-dimensional, electrothermal simulations based on random Voronoi networks have been developed to study the internal heating, current distributions and breakdown effects in ZnO varistors in response to high-voltage pulsing. The simulations allow for dynamic predictions of internal failures and to track the progression of hot-spots and thermal stresses. The focus is on internal grain-size variations and relative disorder including micropores. Our results predict that parameters such as the hold-off voltage, internal temperature, and average dissipated energy density would be higher with more uniform grains. This uniformity is also predicted to produce lower thermal stresses and to allow for the application of longer duration pulses. It is shown that the principal failure mechanism arises from internal localized melting, while thermal stresses are well below the thresholds for cracking. Finally, detrimental effects of micropores have been quantified and shown to be in agreement with experimental trends.