With the rapid development of topology optimization methodology in engineering application, how to deal with the multi-source uncertainties incurs more and more attention. In this study, an efficient single-loop method is proposed for reliability-based topology optimization (RBTO) of coupled thermo-mechanical continuum structure under multi-source uncertainties. To this end, a novel coupled thermo-mechanical RBTO model composed of triple-nested loops is first constructed based on fuzzy and probability theories, which aims to deal with the multi-source uncertainty factors, such as temperature rise fluctuation, thermal load variation, material property uncertainty, and manufacture tolerance. Second, a new mixed RBTO approach with single-loop is adopted to eliminate the nested triple loops, which aims to promote computational efficiency. Finally, the effectiveness and high performance of the proposed method are validated through a cantilever beam, clamped beam, and three-dimensional structure.