Reproduction is a complex phenomenon that is fundamental to all living things. The uterine epithelium of viviparous mammals undergoes vast remodelling to accommodate the developing embryo. There are several levels of placental invasion in mammals that develop a placenta, based on the number of cell layers that separate the developing fetus and maternal blood stream. We investigated whether there are common molecular changes to the uterine surface during pregnancy in Theria by comparing uterine remodelling across several phylogenetic groups with independent origins of endotheliochorial placentae to determine how this placenta type evolved. We tested the generality of uterine remodelling during pregnancy in the marsupial, Sminthopsis crassicaudata (Dasyuridae; the fat-tailed dunnart) and the eutherian, Felis catus (Felidae; the domestic cat) and Dipodomys merriami (Heteromyidae; Merriam’s kangaroo rat). Transmission and Scanning Electron Microscopy were used to study the ultrastructural changes to the uterine epithelium during pregnancy and immunofluorescence microscopy and Western blotting showed that there are common changes to the distribution of key lateral adhesion molecules, desmoglein-2 and E-cadherin. We confirmed that the same ultrastructural and molecular changes to the uterine epithelium are seen in marsupial and eutherian species which represent separate lineages of endotheliochorial placentation. We also determined the effect of the reproductive hormones, progesterone and 17β-oestradiol on the reproductive tract of S. crassicaudata, concluding that the plasma membrane transformation is regulated by the same hormonal mechanisms among therian species. The conclusions from this study support the theory that uterine remodelling and the plasma membrane transformation are crucial for successful pregnancy in viviparous mammals with commonalities in molecular and morphological changes among species.