Rock art of the Middle and Upper Orinoco River in South America is characterised by some of the largest and most enigmatic engravings in the world, including snakes exceeding 40m in length. Here, the authors map the geographic distribution of giant snake motifs and assess the visibility of this serpentine imagery within the Orinoco landscape and Indigenous myths. Occupying prominent outcrops that were visible from great distances, the authors argue that the rock art provided physical reference points for cosmogonic myths, acting as border agents that structured the environment and were central to Indigenous placemaking along the rivers of lowland South America.