Topology optimization methods using discrete elements such as frame elements can provide useful insights into the underlying mechanics principles of products; however, the majority of such optimizations are performed under deterministic conditions. To avoid performance reductions due to later-stage environmental changes, variations of several design parameters are considered during the topology optimization. This paper concerns a reliability-based topology optimization method for frame structures that considers uncertainties in applied loads and nonstructural mass at the early conceptual design stage. The effects that multiple criteria, namely, stiffness and eigenfrequency, have upon system reliability are evaluated by regarding them as a series system, where mode reliabilities can be evaluated using first-order reliability methods. Through numerical calculations, reliability-based topology designs of typical two- or three-dimensional frames are obtained. The importance of considering uncertainties is then demonstrated by comparing the results obtained by the proposed method with deterministic optimal designs.