This paper focuses on an innovative structural system with separated gravity and lateral resisting systems (SGLR system), which is suitable for multi-story prefabricated buildings and demonstrates different seismic performance from the traditional rigid frame system (RF system). Elaborate three-dimensional (3D) finite element models for RF and SGLR systems are established and verified by test results. Based on the numerical models, the load-displacement relationship, force mechanism, energy dissipation capacity, local buckling, and stress and strain distribution of SGLR system are investigated in detail in comparison with RF system. In order to conduct the seismic performance evaluation, four groups of RF and SGLR substructures are designed with different lateral stiffness. Pushover analysis and response spectrum analysis are carried out, and safety factors are calculated on the basis of the incremental N2 method. It is indicated that SGLR system has lower loading capacity, smaller safety margin but larger deformation capability than RF system with the same lateral stiffness. Considering that the inter-story drift ratio is a common design index, more stringent design requirements should be proposed for SGLR system to obtain seismic performance equivalent to that of RF system.