Postimplantation uterine development involves extensive stromal cell proliferation and decidual transformation with polyploidization, which is essential for normal pregnancy establishment. However, it remains largely unknown how stromal proliferation versus decidual polyploidization is differentially regulated during decidualization. Utilizing Wnt6-mutant mice, we show here that Wnt6 deficiency impairs stromal cell proliferation without much adverse effects on decidual polyploidization. Applying a primary stromal cell culture model, we further reveal that loss of Wnt6 prolongs the cell cycle length via downregulating cyclin B1 expression, thus attenuating stromal cell proliferation. Our study provides the first genetic evidence that Wnt6 is critical for normal stromal cell proliferation in mice, highlighting the concept that there are differential machineries governing the process of stromal cell proliferation versus decidual transformation during early pregnancy. This finding has high clinical relevance because Wnt signaling is known to be important for human implantation and endometrial function.