Mechanical failures in the operating stacks of solid oxide fuel cells (SOFCs) are frequently related to thermal stresses generated by a temperature gradient and its variation. In this study, a computational fluid dynamics (CFD) model is developed and further applied in full-size SOFC stacks, which are fully coupled and implemented for analysis of heat flow electrochemical phenomena, aiming to predict thermal stress distribution. The primary object of the present investigation is to explore features and characteristics of the thermal stress influenced by electrochemical reactions and various transport processes within the stacks. It is revealed that the volume ratio of the higher thermal stress region differs nearly 30% for different stack flow configurations; the highest probability of potential failure appears in the cell cathodes; the more cells applied in the stack, the greater the difference in the predicted temperature/thermal stress between the cells; the counter-flow stack performs the best in terms of output power, but the predicted thermal stress is also higher; the cross-flow stack exhibits the lowest thermal stress and a lower output power; and although the temperature and thermal stress distributions are similar, the differences between the unit cells are bigger in the longer stacks than those predicted for shorter stacks. The findings from this study may provide a useful guide for assessing the thermal behavior and impact on SOFC performance.