Advanced nonlinear finite element analysis (FEA) enables the Direct Design Method (DDM) of a frame by computational analysis in place of designing members and connections to codified specific equations. The Direct Design Method has become a feasible design option and attracted increasing attention from the research community, designers and code writers. One of the research challenges of adopting the DDM is to develop a system-based limit state design criterion to ensure a stipulated level of structural reliability, similar to that of member-based design methods. The present paper derives the system resistance factors suitable for the DDM of typical spatial moment-resisting steel frames comprising rigid connections and members of compact sections under wind and gravity loads. The interaction of the system resistance factor and frame reliability is established, which can serve as a basis for the code writers to choose the appropriate system resistance factors for the DDM.