America's first urban centers may have been located in the Supe Valley, Peru. After investigating the location and the orientation of the main built structures, we show that it is not only the presence of the Supe River that determines their orientation but also that astronomical relationships within the orientation of the buildings dictate their setting within the valley. The southernmost position of moonrise on the horizon seems to be the most important astronomical target. There is the possibility of a trend toward attributing greater importance to the June solstice sunrise and the rising of certain stars or asterisms. These orientations could relate to specific moments throughout the year, in particular to seasonal rains, subsequent river flooding, and agricultural cycles. This is one of the earliest examples of the interaction of land- and skyscapes in human cultures and indeed the first in the Americas.