In this study, in order to accurately predict the nuclear fuel cladding’s ballooning and burst behavior during Loss of Coolant Accident (LOCA) of a nuclear reactor, modeling of high temperature and anisotropic creep behavior of the cladding was carried out and simulation for prediction of the cladding’s behavior during the LOCA was performed through development of multi-dimensional finite element analysis platform. Steady-state creep model was introduced to model the high temperature creep behavior and the cladding’s anisotropy was modeled by using Hill’s anisotropic yield function. In addition, a relationship between the creep coefficient and the anisotropy coefficients was deduced. To accurately predict the cladding’s complex thermo-mechanical behavior, a finite element analysis platform which is based on thermo-mechanical coupled analysis was developed. The platform reflects nuclear fuel specific models such as gap heat transfer, temperature and burnup dependent material properties, and high temperature anisotropic creep. The developed platform was verified through various numerical examples and it was found that the developed platform correctly calculated each example. In addition, to confirm its validity as a numerical tool for the simulation of the LOCA, the developed platform was also validated by comparing with an experiment which postulates the LOCA. It was found that the developed platform’s prediction showed a good agreement with the experimental results. Moreover, to verify the modeling methodology proposed in this study, accuracy comparison was made by comparing with conventional methods which are isotropic material assumption, a method used in an existing nuclear fuel rod analysis code, and one dimensional analysis method. From the comparison results, it was found that the present methodology could predict the ballooning and burst more accurately and showed more realistic behavior of the cladding that the other methods by considering the cladding’s anisotropy in a more consistent and reasonable manner. Thus, it was concluded that the present study will be able to improve understandings of the nuclear fuel cladding’s thermo-mechanical behavior during the LOCA, and will help to revise the nuclear safety regulations in line with the trend to incorporate more realistic behavior of the nuclear fuel rod into the regulations.