Leukemia inhibitor factor (LIF)-Stat3 and Wnt/beta-catenin signaling pathways play an important role in promoting mouse embryonic stem cell (mESC) self-renewal. The common downstream targets of these two pathways, however, have never been identified. In this study, we found that the LIF-Stat3 and Wnt/beta-catenin signaling pathways converge on a common gene called Sp5 to promote mESC self-renewal. Forced Sp5 expression can reproduce partial effects of Wnt/beta-catenin signaling but mimics most features of LIF-Stat3 signaling to maintain mESCs in culture. Our results suggest that Sp5 is an important component of the regulatory network governing mESC pluripotency.