We analyzed, from a cultural astronomy perspective, the relationship between the orientations of five mound sites and different astronomical events in the lowland region of Uruguay. We found significant relationships between the orientations of the mounds and the Southern Cross/Milky Way and the full Moon during the winter solstice ca. 3000 years BP. These relationships, meanings and senses to different native peoples of South America were explored from the literature of travelers’ and naturalists’ chronicles, alongside the ethnohistorical, ethnographic and archaeological literature. In particular, we highlighted the link among those peoples of the area of the Southern Cross/ Milky Way with a mythical Ñandú (Rhea americana). Such an interpretation has allowed us to raise the possibility that we are being faced with the integration of knowledge of the sky in the form of the social construction of inhabited space and the configuration of the landscape.