In this paper, the concentrations of fission products and fuel isotopes as well as the changes of the thermo-neutronic parameters of the Bushehr’s VVER-1000 reactor were studied during the initial startup and the first cycle. In order to perform the time-dependent cell calculations and obtain the concentration of fuel elements, the WIMSD5-B code was used. Besides, by utilizing the CITATION-LDI2 code, the effective multiplication factor and the thermal power distribution of the reactor were calculated. A computer program (WERL code) was designed in order to perform accurate calculation of the temperature distribution of the reactor core. For this purpose, the Ross–Stoute, Weisman, and Lee–Kesler models were used for calculating of the gap conductance coefficient, fission gas release and gap pressure, respectively. The results demonstrated that in designing the startup process, in addition to the role considered for overcoming the power defects and in preparing the required conditions for performing the safety-assurance tests, the flattening of the reactor’s power must be taken into account. Comparison between the results of this modeling and the final safety analysis report of this reactor showed that the results presented in this paper are satisfactorily accurate.