In human pregnancy, recognition of a developing fetus within the uterus is essential to maintain uterine quiesence and support the embryo through an extended gestation. In most marsupials (with the exception of macropods), pregnancy is shorter than the estrus cycle, and for this reason it has been assumed that recognition of pregnancy is not necessary, and was a trait that evolved in the first eutherian (placental) mammals. To investigate whether there is uterine recognition of pregnancy in early live bearing mammals, we examined reproduction in the grey short tailed opossum (Monodelphis domestica) a marsupial with what is assumed to have the most pleiotropic mode of pregnancy. We examined the morphological and gene expression changes in the uterus of females in the estrus cycle, and compared these to the observed changes during pregnancy. We found that while the morphology of the uterus undergoes substantial changes in pregnancy, these changes occur in a programmed fashion during estrus, and for the most part do not appear to be impacted by the presence of a fetus. However, transcriptionally we saw big differences between the uterus of pregnant and estrus animals. Gene ontology analysis shows us that the genes up-regulated due to the presence of a fetus are involved in macromolecular transport, inflammation, and metabolic activity. Our results suggest that while the uterus exhibits programmed changes in response to ovulation, the transcriptional landscape of pregnancy responds to the presence of a fetus, and upregulates suites of genes that may be essential for fetal support. These results are consistent with uterine recognition of pregnancy being an older feature dating back to the origin of live birth in mammals.