Various self-centering structural systems were developed and investigated for reducing residual inter-story drifts of the traditional aseismic structural system by achieving full or partial self-centering behaviors under earthquakes in the past twenty years. However, limited research was conducted to investigate the life-cycle benefits of the full and partial self-centering structural systems on the life-cycle span, figuring out a more cost-effective solution for enhancing the building’s seismic resilience. This paper aims to comprehensively investigate the life-cycle benefits of full and partial self-centering structural systems compared to conventional buckling-restrained braced frames (BRBFs) using the life-cycle cost estimation method. The influences of the residual inter-story drift limit for demolition, the initial cost of emerging self-centering members, the value of building contents, and the discount rate were particularly investigated. To this end, three building structures with BRBFs and full and partial self-centering structural systems were designed to achieve the same capacity for controlling maximum inter-story drifts. Comprehensive dynamic analyses were performed to generate engineering parameters under different seismic intensities and the modeling uncertainties were properly considered through Monte Carlo simulation. The revised HAZUS loss calculation method was adopted to investigate the seismic annual loss (SAL) and life-cycle cost. The analysis results indicate that the partial self-centering behavior would be a better choice than the full self-centering behavior for developing the self-centering structural systems to achieve better life-cycle benefits. Moreover, it is essential and urgent to reduce the initial costs of self-centering structural members and control the floor acceleration responses for increasing the life-cycle benefits of self-centering structural systems and promoting their practical applications.