The strong column-weak beam failure mode of reinforced concrete (RC) frame structures is one of the most important targets of structural seismic design and is primarily realized by a reasonable column overdesign factor (COF). However, most RC frame structures in previous earthquakes were often subjected to strong beam-weak column failure modes. To address this issue, the RC frame with a strong column-weak beam failure mode and a typical strong beam-weak column RC frame in the 2022 Ms 6.8 Luding earthquake were intensively studied in this study. The differences between the two failure modes of the RC frame structure were comparatively analyzed at both the overall structure and member levels. A numerical simulation was conducted to obtain the structural response under actual ground motion. Finally, a probabilistic analysis method was adopted to process the COF data of the RC frame joints. The results indicate that the structural safety redundancy of the RC frame with the undesired failure mode cannot be fully utilized, whereas the RC frame with the strong column-weak beam failure mode allows more structural members to participate in the energy dissipation through a complex redistribution mechanism of internal forces. Damage to the infill wall further mitigates the degree of damage to the main structure and reduces the risk of soft-story failure. The COF of the actual RC frame structure shows a non-uniform distribution, and it is recommended that the COF be higher than 1.5 for the seismic design of the structure following the Chinese code.