The snake is a potent entity in many cultures across the world, and is a noticeable global theme in rock art and inscribed landscapes. We mobilise our long-term ethnographic research with southern African KhoeSan peoples to situate and interpret the presence of snake motifs in the region's rock art. We contextualise the snake as a transformative ontological mediator between everyday and "entranced" KhoeSan worlds (those associated with "altered states of consciousness"), to weave together both mythological and shamanistic interpretations of southern African rock art. Ethnographic explorations of experiences of snakes as both an aspect of natural history and the physical environment, and as embodiments of multiplicitous and mythical meaning by which to live and understand life, shed light on the presence of snakes and associated snake-themes in southern African rock art. By drawing on ethnographic material, and in conjunction with review of literature, we highlight a dynamic assemblage of extant associations between snakes, rain, water, fertility, blood, fat, transformation, dance and healing. We suggest that these extant associations have explanatory potential for understanding the meaning of these themes in the rock art created by the ancestors of contemporary KhoeSan peoples. Our paper contributes to a live debate regarding the interpretive relevance of ethnography for understanding rock art representations from the past.