Although much is known about the molecular signaling during implantation, the uterine 3D architecture that facilitates embryo development remains unknown. Imaging the mouse embryo and the uterine milieu simultaneously we uncovered patterns of embryo movement and dynamic shape changes in the uterine lumen and glands in preparation for implantation. When applied to mouse mutants with known implantation defects, this method detected striking peri-implantation abnormalities in uterine morphology that cannot be visualized by histology. Analyzing the uterine and embryo structure in 3D for genetic mutants, hormonal perturbations and pregnancies treated with pathway inhibitors is helping us uncover novel molecular pathways and global structural changes that contribute to successful implantation of an embryo. Our studies have implications for understanding how structure-based embryo-uterine communication is key to determining an optimal implantation site, which is necessary for the success of a pregnancy.